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Corrêa CAP, Chagas PS, Baroni M, Andrade AF, de Paula Queiroz RG, Suazo VK, Veiga Cruzeiro GA, Fedatto PF, Antonio DSM, Brandalise SR, Yunes JA, Panepucci RA, Carlotti Junior CG, de Oliveira RS, Neder L, Tone LG, Valera ET, Scrideli CA. miR-512-3p as a Potential Biomarker of Poor Outcome in Pediatric Medulloblastoma. CEREBELLUM (LONDON, ENGLAND) 2025; 24:72. [PMID: 40128489 DOI: 10.1007/s12311-025-01812-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/25/2025] [Indexed: 03/26/2025]
Abstract
The tumorigenesis of medulloblastoma (MB), the most frequent malignant brain tumor in children, is not completely known. MicroRNA (miRNA) expression profiles have been associated with human cancers; however, the role played by miRNAs in pediatric MB has been poorly explored. Global miRNA expression in MB and non-neoplastic cerebellum samples was evaluated by microarray assay. Nine miRNAs (miR-31-5p, -329, -383, -433, -485-3p, -485-5p, -491, -512-3p, and 539-5p) in 51 pediatric MB and 7 pediatric non-neoplastic cerebellum samples were chosen for validation by qRT-PCR. The validated miRNAs were less expressed in the MB samples than in the non-neoplastic controls. In our cohort of patients, higher miR-512-3p expression was associated with incomplete degree of resection, classification as high risk, classification as group 4, and poor overall survival. In silico analysis in an independent cohort of MB patients identified that some of the miR-512-3p target genes were also correlated with prognostic features. Our results have shown that miR-512-3p could be associated with poor clinical outcomes in pediatric MB, suggesting that miR-512-3p is a potential biomarker of prognosis.
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Affiliation(s)
| | - Pablo Shimaoka Chagas
- Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Mirella Baroni
- Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | | | - Rosane Gomes de Paula Queiroz
- Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14048-900, Brazil
| | - Veridiana Kiill Suazo
- Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14048-900, Brazil
| | | | - Paola Fernanda Fedatto
- Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14048-900, Brazil
| | | | | | - José Andres Yunes
- Boldrini Children's Center, Laboratory of Molecular Biology, Campinas, Brazil
| | | | | | | | - Luciano Neder
- Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Luiz Gonzaga Tone
- Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14048-900, Brazil
| | - Elvis Terci Valera
- Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14048-900, Brazil
| | - Carlos Alberto Scrideli
- Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
- Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14048-900, Brazil.
- National Science and Technology Institute for Children's Cancer Biology and Pediatric Oncology - INCT BioOncoPed, Porto Alegre, Brazil.
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Gong Y, Fu W. Reversible role of MIR654/3P and MIR9/3P in pathogenesis of Epstein-Barr virus-negative, but not Epstein-Barr virus-positive, Burkitt lymphoma. J Leukoc Biol 2025; 117:qiae237. [PMID: 39446559 DOI: 10.1093/jleuko/qiae237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 09/13/2024] [Accepted: 10/23/2024] [Indexed: 10/26/2024] Open
Abstract
The role of MIR654 in Burkitt lymphoma (BL) and whether it impacts expression of MYC and its downstream activated MIR9 is not known. Expression of MYC, MYCN, MYCL, MIR9/3P, MIR654/5P, and MIR654/3P was assessed by quantitative reverse-transcription polymerase chain reaction in biopsy samples from Epstein-Barr virus-negative (EBV-) and EBV+ BL patients and BL cell lines. Effects of modulation of MIR9/3P and MIR654/3P on cell proliferation, apoptosis, and chemosensitivity were evaluated. Luciferase reporter assay was performed to validate the putative target of MIR654/5P. Effects of MIR9/3P and MIR654/3P on tumor burden and disease outcome were evaluated using xenograft model of BL. Expression of MYC, MYCN, and MIR9/3P was higher in all BL patient samples and cell lines. Expression of MIR654/3P was downregulated in EBV- BL patient samples and cell lines compared with either noncancer lymphoid-reactive hyperplasia or EBV+ samples and cell lines. Additionally, MIR654/3P overexpression inhibited cell proliferation, induced apoptosis, and increased chemosensitivity in EBV- BL cell lines. Luciferase reporter assay confirmed that MYC is a target of MIR654/3P in both EBV- and EBV+ BL cell lines; however, the effect of MIR654/3P-mediated targeting of MYC is overridden in EBV+ cells. Administration of MIR654/3P mimic or MIR9/3P antagomir in the xenograft model decreased tumor burden and increased survival. Combined intervention with MIR654/3P mimic and MIR9/3P antagomir had synergistic action on decreasing tumor burden and improving disease outcome. MIR654/3P, as a putative tumor suppressor in EBV- BL, collaborating with MIR9/3P might serve as a therapeutic agent to treat EBV- BL patients in combination with existing chemotherapy and immunotherapy regimes.
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Affiliation(s)
- Yu Gong
- Department of Hematology, Huainanchaoyang Hospital, No. 15 Renmin South Road, Tianjia 'an District, Huainan 232007, Anhui, China
- Department of Hematology, First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei 230022, Anhui, China
| | - Wenhua Fu
- Cancer Center, Huainanchaoyang Hospital, No. 15 Renmin South Road, Tianjia 'an District, Huainan 232007, Anhui, China
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Elshafie NO, Gribskov M, Lichti NI, Sayedahmed EE, Childress MO, Pires dos Santos A. MicroRNAs implicated in canine diffuse large B-cell lymphoma prognosis. FEBS Open Bio 2024; 14:1899-1913. [PMID: 39218619 PMCID: PMC11532975 DOI: 10.1002/2211-5463.13887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 07/16/2024] [Accepted: 08/14/2024] [Indexed: 09/04/2024] Open
Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin lymphoma (NHL) in domestic dogs, with many similarities to its human counterpart. The progression of the disease is rapid, and treatment must be initiated early to achieve cancer remission and extend life. This study examined the relationship between progression-free survival (PFS) and microRNA (miRNA) expression in dogs with DLBCL. miRNAs are small non-coding RNA molecules that typically regulate gene expression post-transcriptionally. They are involved in several pathophysiological processes, including the growth and progression of cancer. Based on the analysis of small RNA sequencing (sRNA-seq) data, we validated a group of miRNAs in lymph nodes from 44 DLBCL-affected dogs with known outcomes. We used quantitative PCR to quantify their expression and report a specific subset of miRNAs is associated with decreased PFS in dogs with DLBCL. The miR-192-5p and miR-16-5p expression were significantly downregulated in dogs with increased PFS. These results indicate that miRNA profiling may potentially identify dogs with DLBCL that will experience poor outcomes following treatment. Identifying specific miRNAs that correlate with the progression of canine DLBCL could aid the development of individualized treatment regimens for dogs.
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Affiliation(s)
- Nelly O. Elshafie
- Department of Comparative PathobiologyPurdue UniversityWest LafayetteINUSA
| | - Michael Gribskov
- Department of Biological SciencesPurdue UniversityWest LafayetteINUSA
| | | | | | - Michael O. Childress
- Department of Veterinary Clinical SciencesPurdue UniversityWest LafayetteINUSA
- Purdue Institute for Cancer ResearchPurdue UniversityWest LafayetteINUSA
| | - Andrea Pires dos Santos
- Department of Comparative PathobiologyPurdue UniversityWest LafayetteINUSA
- Department of Biological SciencesPurdue UniversityWest LafayetteINUSA
- Bindley Bioscience CenterPurdue UniversityWest LafayetteINUSA
- Department of Veterinary Clinical SciencesPurdue UniversityWest LafayetteINUSA
- Purdue Institute for Cancer ResearchPurdue UniversityWest LafayetteINUSA
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Lotfi E, Kholghi A, Golab F, Mohammadi A, Barati M. Circulating miRNAs and lncRNAs serve as biomarkers for early colorectal cancer diagnosis. Pathol Res Pract 2024; 255:155187. [PMID: 38377721 DOI: 10.1016/j.prp.2024.155187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 01/28/2024] [Accepted: 01/31/2024] [Indexed: 02/22/2024]
Abstract
BACKGROUND Colorectal cancer (CRC), the third most prevalent and lethal disease, accounted for approximately 1.9 million new cases and claimed nearly 861,000 lives in 2018. It is imperative to develop a minimally invasive diagnostic technique for early identification of CRC. This would facilitate the selection of patient populations most suitable for clinical trials, monitoring disease progression, assessing treatment effectiveness, and enhancing overall patient care. Utilizing blood as a biomarker source is advantageous due to its minimal discomfort for patients, enabling better integration into clinical and follow-up trials. Recent findings indicate that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are detectable in the blood of cancer patients, proving crucial in diagnosing various malignancies. METHODS In this case-control study, we collected plasma samples from 30 patients diagnosed with colorectal cancer (CRC) and 30 healthy volunteers. Following RNA extraction, we measured the expression levels of specific biomolecules, including miR-410, miR-211, miR-139, miR-197, lncRNA UICLM, lncRNA FEZF1-AS1, miR-129, lncRNA CCAT1, lncRNA BBOX1-AS1, and lncRNA LINC00698, using real-time quantitative polymerase chain reaction (RT-qPCR). The obtained data underwent analysis using the Mann-Whitney test for non-parametric data and the T-test for parametric data. RESULTS The level of miR-410, miR-211, miR-139, miR-197, lncRNA UICLM, lncRNA FEZF1-AS1 were significantly higher in patients with CRC than healthy controls (p < .05). Meanwhile, the level of miR-129, lncRNA CCAT1, lncRNA BBOX1-AS1, and lncRNA LINC00698 were higher in healthy controls than in CRC patients (p < .05). CONCLUSION MicroRNA (miRNA) and long noncoding RNAs (lncRNAs) have recently emerged as detectable entities in the blood of cancer patients, playing crucial roles in diagnosing various malignancies. However, their specific relevance in the diagnosis of colorectal cancer (CRC) remains underexplored. This study aimed to investigate miRNA and lncRNA profiles in the plasma fraction of human blood to discern significant differences in content and expression levels between CRC patients and healthy individuals. Our cohort comprised 30 CRC patients and 30 healthy controls, with no statistically significant differences (p < 0.05) in age or gender observed between the two groups. Noteworthy is the uniqueness of our study, as we identified a panel of three significant microRNAs and one significant lncRNA, providing a more reliable prediction compared to existing molecular markers in diagnosing CRC. The four genes examined, including miR-211, miR-129, miR-197, and lncRNA UICLM, demonstrated impeccable results in terms of sensitivity and specificity, suggesting their potential candidacy for inclusion in diagnostic panels. Further validation in a larger statistical population is recommended to confirm the robustness of these genes as promising markers for colorectal cancer diagnosis.
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Affiliation(s)
- Ehsan Lotfi
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical sciences, Tehran, Iran
| | - Azam Kholghi
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical sciences, Tehran, Iran
| | - Fereshteh Golab
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Mohammadi
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical sciences, Tehran, Iran
| | - Mahmood Barati
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical sciences, Tehran, Iran.
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Guo X, Zhang J, Zeng J, Guo Y, Zhao L. MiR-525-5p inhibits diffuse large B cell lymphoma progression via the Myd88/NF-κB signaling pathway. PeerJ 2023; 11:e16388. [PMID: 37953776 PMCID: PMC10634338 DOI: 10.7717/peerj.16388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 10/11/2023] [Indexed: 11/14/2023] Open
Abstract
Diffuse large B-cell lymphoma (DLBCL) is a B-cell lymphoma with a high degree of aggressiveness. Recently, evidence has shown that miR-525-5p is decreased in DLBCL, suggesting its possible involvement in tumor progression. In this study, miR-525-5p suppressed proliferation, invasion and clonogenicity, and increased apoptosis of U2932 cells, whereas miR-525-5p silencing enhanced tumor cell growth. Next, miR-525-5p targets the 3'-UTR of Myd88, and Myd88 protein was increased in lymphoma tissues. Similar to the miR-525-5p mimic, Myd88 siRNA suppressed proliferation, invasion, and clonogenicity, and enhanced apoptosis of U2932 cells. We observed that Myd88 reversed the inhibitory effect of miR-525-5p on tumor cell growth by transfecting cells with miR-525-5p mimics alone or together with Myd88 overexpression vector. In addition, in vivo studies have shown that compared to the control group, U2932 cells with upregulated miR-525-5p expression have a reduced ability to induce tumor formation. In conclusion, our results demonstrate that miR-525-5p inhibits the progression of DLBCL through the Myd88/NF-κB pathway, which largely fills the gap of previous studies, and our results may provide a new reference for the targeted treatment of DLBCL.
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Affiliation(s)
- Xiuchen Guo
- Department of Hematology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Jingbo Zhang
- Department of Hematology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Jingya Zeng
- Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yiwei Guo
- Department of Hematology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Lina Zhao
- Department of Hematology, Harbin Medical University Cancer Hospital, Harbin, China
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Peng YY, Zhang HB, Wang X, Xiao Q, Guo SL. The biomarkers of key miRNAs and gene targets associated with extranodal NK/T-cell lymphoma. Open Med (Wars) 2022; 17:124-134. [PMID: 35071774 PMCID: PMC8729226 DOI: 10.1515/med-2021-0409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 11/27/2021] [Accepted: 11/27/2021] [Indexed: 11/15/2022] Open
Abstract
Gene expression profiling studies have shown the pathogenetic role of oncogenic pathways in extranodal natural killer/T-cell lymphoma (ENKL). In this study, we aimed to identify the microRNAs (miRNAs) playing potential roles in ENKL, and to evaluate the genes and biological pathways associated to them. Gene expression profiles of ENKL patients were acquired from the gene expression omnibus (GEO) database. Most differentially expressed (DE)-miRNAs were identified in ENKL patients using limma package. Gene targets of the DE-miRNAs were collected from online databases (miRDB, miRWalk, miRDIP, and TargetScan), and used in Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses on Database for annotation, visualization, and integrated discovery database, and then used in protein–protein interaction (PPI) analysis on STRING database. Hub genes of the PPI network were identified in cytoHubba, and were evaluated in Biological networks gene ontology. According to the series GSE31377 and GSE43958 from GEO database, four DE-miRNAs were screened out: hsa-miR-363-3p, hsa-miR-296-5p, hsa-miR-155-5p, and hsa-miR-221-3p. Totally 164 gene targets were collected from the online databases, and used in the GO and KEGG pathway analyses and PPI network analysis. Ten hub genes of the PPI network were identified: AURKA, TP53, CDK1, CDK2, CCNB1, PLK1, CUL1, ESR1, CDC20, and PIK3CA. Those hub genes, as well as their correlative pathways, may be of diagnostic or therapeutic potential for ENKL, but further clinical evidence is still expected.
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Affiliation(s)
- Yin-yin Peng
- Department of Hematology Medicine, The First Affiliated Hospital of Chongqing Medical University , Chongqing , 400016 , China
| | - Hong-bin Zhang
- Department of Hematology Medicine, The First Affiliated Hospital of Chongqing Medical University , Chongqing , 400016 , China
| | - Xin Wang
- Department of Hematology Medicine, The First Affiliated Hospital of Chongqing Medical University , Chongqing , 400016 , China
| | - Qing Xiao
- Department of Hematology Medicine, The First Affiliated Hospital of Chongqing Medical University , Chongqing , 400016 , China
| | - Shu-liang Guo
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University , Chongqing 400016 , China
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Wang J, Wang C, Yang L, Li K. Identification of the critical genes and miRNAs in hepatocellular carcinoma by integrated bioinformatics analysis. Med Oncol 2022; 39:21. [PMID: 34982264 DOI: 10.1007/s12032-021-01622-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 11/29/2021] [Indexed: 12/24/2022]
Abstract
Hepatocellular carcinoma (HCC) is a global health problem with complex etiology and pathogenesis. Microarray data are increasingly being used as a novel and effective method for cancer pathogenesis analysis. An integrative analysis of genes and miRNA for HCC was conducted to unravel the potential prognosis of HCC. Two gene microarray datasets (GSE89377 and GSE101685) and two miRNA expression profiles (GSE112264 and GSE113740) were obtained from Gene Expression Omnibus database. A total of 177 differently expressed genes (DEGs) and 80 differently expressed miRNAs (DEMs) were screened out. Functional enrichment of DEGs was proceeded by Clue GO and these genes were significantly enriched in the chemical carcinogenesis pathway. A protein-protein interaction network was then established on the STRING platform, and ten hub genes (CDC20, TOP2A, ASPM, NCAPG, AURKA, CYP2E1, HMMR, PRC1, TYMS, and CYP4A11) were visualized via Cytoscape software. Then, a miRNA-target network was established to identify the hub dysregulated miRNA. A key miRNA (hsa-miR-124-3p) was filtered. Finally, the miRNA-target-transcription factor network was constructed for hsa-miR-124-3p. The network for hsa-miR-124-3p included two transcription factors (TFs) and five targets. These identified DEGs and DEMs, TFs, targets, and regulatory networks may help advance our understanding of the underlying pathogenesis of HCC.
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Affiliation(s)
- Jun Wang
- School of Biological Food and Environment, Hefei University, Hefei, 230601, China.
| | - Chuyan Wang
- School of Biological Food and Environment, Hefei University, Hefei, 230601, China
| | - Liuqing Yang
- School of Biological Food and Environment, Hefei University, Hefei, 230601, China
| | - Kexin Li
- School of Biological Food and Environment, Hefei University, Hefei, 230601, China
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Liang Z, Li X, Duan F, Song L, Wang Z, Li X, Yang P, Li L. Protein tyrosine phosphatase non-receptor type 12 (PTPN12), negatively regulated by miR-106a-5p, suppresses the progression of hepatocellular carcinoma. Hum Cell 2021; 35:299-309. [PMID: 34784010 DOI: 10.1007/s13577-021-00627-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 10/01/2021] [Indexed: 12/24/2022]
Abstract
Protein tyrosine phosphatase non-receptor type 12 (PTPN12) is abnormally expressed in many human cancers. However, its role in hepatocellular carcinoma (HCC) is indeterminate. In this study, immunohistochemistry and Western blot were adopted to detect PTPN12 protein expression in HCC tissues and cell lines. MiR-106a-5p and PTPN12 mRNA expressions were determined by quantitative real-time polymerase chain reaction (qRT-PCR). siRNA was used to knockdown PTPN12 expression in HCC cells, and the multiplication, migration, and invasion of HCC cells were determined by cell counting kit 8 (CCK-8) and Transwell assays. The interaction between PTPN12 and miR-106a-5p was verified by dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. In the present study, we demonstrated that PTPN12 expression in HCC tissues and cells was significantly decreased, which was associated with the tumor size, TNM stage, and lymph node metastasis of HCC patients. Functionally, knocking down PTPN12 significantly promoted the multiplication, migration, invasion, and epithelial-mesenchymal transition (EMT) of HCC cells. PTPN12 was identified as the direct target of miR-106a-5p, and its expression was negatively modulated by miR-106a-5p. Besides, PTPN12 counteracted the promoting effects of miR-106a-5p on the viability, migration, invasion, and EMT of HCC cells. In conclusion, this study substantiates that PTPN12 inhibits the growth, migration, invasion, and EMT of HCC cells, and miR-106a-5p contributes to its dysregulation in HCC.
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Affiliation(s)
- Zhanqiang Liang
- Department of Hepatobiliary Surgery, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou, 450007, Henan, China
| | - Xingxing Li
- Department of General Surgery, Xinzheng Public People's Hospital, Xinzheng, Zhengzhou, 451150, Henan, China
| | - Fei Duan
- Department of Hepatobiliary Surgery, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou, 450007, Henan, China
| | - Liming Song
- Department of Hepatobiliary Surgery, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou, 450007, Henan, China
| | - Zhongzhen Wang
- Department of General Surgery, Xinzheng Public People's Hospital, Xinzheng, Zhengzhou, 451150, Henan, China
| | - Xuemin Li
- Department of Hepatobiliary Surgery, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou, 450007, Henan, China
| | - Pengsheng Yang
- Department of Hepatobiliary Surgery, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou, 450007, Henan, China
| | - Liantao Li
- Department of General Surgery, Xinzheng Public People's Hospital, Xinzheng, Zhengzhou, 451150, Henan, China.
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Long Z, Gong F, Li C. MiR-532-3p Suppresses Nucleus Pulposus Cells Proliferation and Extracellular Matrix Production, Promotes Cell Apoptosis via Targeting High Mobility Group AT-Hook 2. J BIOMATER TISS ENG 2021. [DOI: 10.1166/jbt.2021.2685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
The present study aimed to investigate the function and mechanism of microRNA (miR)-532-3p in intervertebral disc degeneration (IDD). Further, whether miR-532-3p regulates HMGA2 in nucleus pulposus (NP) cells was explored. We collected human nucleus pulposus (NP) tissues from the patients
with IDD, and detected miR-532-3p in NP tissues using RT-qPCR. MiR-532-3p mimic and inhibitor were constructed, and they were transfected into the human nucleus pulposus cells (HNPCs) by Lipofectamine 3000. MTT assay was conducted to determine cell proliferation. Cell apoptosis and extracellular
matrix remodeling were examined by flow cytometric, Caspase 3/8 Assay Kits and Western blot. A dual-luciferase reporter assay was applied to investigate whether miR-532-3p targets High mobility group AT-hook 2 (HMGA2). We found miR-532-3p expression level was significantly increased in NP
tissues of IDD patients, comparing with the controls. MiR-532-3p exerted an inhibitory effect on HNPCs proliferation; however, cell apoptosis and the degradation of extracellular matrix were induced by miR-532-3p. MiR-532-3p directly targets HMGA2, and HMGA2 overexpression reversed the role
of miR-532-3p mimic in HNPCs proliferation, apoptosis, and extracellular matrix remodeling. Our study is the first to report that miR-532-3p might suppress NP cell proliferation, promote cell apoptosis and inhibit ECM production of NP cells via targeting HMGA2, thus facilitating the progression
of IDD. MiR-532-3p was supposed to be a novel target for the treatment of IDD.
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Affiliation(s)
- Zhisheng Long
- Department of Orthopaedics, Jiangxi Provincial People’s Hospital, Nanchang 360000, Jiangxi, China
| | - Feipeng Gong
- Department of Orthopaedics, Jiangxi Provincial People’s Hospital, Nanchang 360000, Jiangxi, China
| | - Chen Li
- Department of Orthopaedics, Jiangxi Provincial People’s Hospital, Nanchang 360000, Jiangxi, China
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Tang M, Liu C, Liu D, Liu J, Liu J, Deng L. PMDFI: Predicting miRNA-Disease Associations Based on High-Order Feature Interaction. Front Genet 2021; 12:656107. [PMID: 33897768 PMCID: PMC8063614 DOI: 10.3389/fgene.2021.656107] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 02/18/2021] [Indexed: 12/23/2022] Open
Abstract
MicroRNAs (miRNAs) are non-coding RNA molecules that make a significant contribution to diverse biological processes, and their mutations and dysregulations are closely related to the occurrence, development, and treatment of human diseases. Therefore, identification of potential miRNA–disease associations contributes to elucidating the pathogenesis of tumorigenesis and seeking the effective treatment method for diseases. Due to the expensive cost of traditional biological experiments of determining associations between miRNAs and diseases, increasing numbers of effective computational models are being used to compensate for this limitation. In this study, we propose a novel computational method, named PMDFI, which is an ensemble learning method to predict potential miRNA–disease associations based on high-order feature interactions. We initially use a stacked autoencoder to extract meaningful high-order features from the original similarity matrix, and then perform feature interactive learning, and finally utilize an integrated model composed of multiple random forests and logistic regression to make comprehensive predictions. The experimental results illustrate that PMDFI achieves excellent performance in predicting potential miRNA–disease associations, with the average area under the ROC curve scores of 0.9404 and 0.9415 in 5-fold and 10-fold cross-validation, respectively.
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Affiliation(s)
- Mingyan Tang
- School of Computer Science and Engineering, Central South University, Changsha, China
| | - Chenzhe Liu
- School of Computer Science and Engineering, Central South University, Changsha, China
| | - Dayun Liu
- School of Computer Science and Engineering, Central South University, Changsha, China
| | - Junyi Liu
- School of Computer Science and Engineering, Central South University, Changsha, China
| | - Jiaqi Liu
- School of Computer Science and Engineering, Central South University, Changsha, China
| | - Lei Deng
- School of Computer Science and Engineering, Central South University, Changsha, China
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Xiong G, Zhang J, Zhang Y, Pang X, Wang B, Zhang Y. Circular RNA_0074027 participates in cell proliferation, apoptosis and metastasis of colorectal cancer cells through regulation of miR‑525‑3p. Mol Med Rep 2021; 23:324. [PMID: 33760126 PMCID: PMC7974509 DOI: 10.3892/mmr.2021.11963] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 01/21/2021] [Indexed: 12/25/2022] Open
Abstract
The present study aimed to elucidate the biological function of circular RNAs (circRNA) 0074027 in colorectal cancer (CRC). The expression of circRNA‑0074027 in CRC tissues and cells was determined by reverse transcription‑quantitative PCR. The in vitro experiments, including Cell Counting Kit‑8 (CCK‑8) assay, 5‑Ethynyl‑2'‑deoxyuridine assay, flow cytometry and Transwell assay, were applied to evaluate cell proliferation, apoptosis and metastasis ability respectively following downregulation of circRNA‑0074027. The correlation between circRNA‑0074027 and micro (mi)RNA‑525‑3p was determined via dual‑luciferase reporter assay. Finally, western blotting was used to explore the possible regulatory mechanism. CircRNA‑0074027 was upregulated in CRC tissues, while miR‑525‑3p expression was reduced. In addition, patients with CRC and circRNA‑0074027 overexpression were more likely to have low tumor differentiation, lymph node metastasis and advanced TMN stage. Deletion of circRNA‑0074027 could suppress cell proliferation and metastasis through up-regulating p53 expression and forbidding epithelial‑mesenchymal transition signaling pathway. The addition of miRNA‑525‑3p inhibitors could reverse the anti‑tumor effects induced by the deletion of circRNA‑0074027. The downregulation of cirRNA_0074027 inhibited tumor progression via sponging miR‑525‑3p, which could be a promising treatment bio‑marker for CRC.
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Affiliation(s)
- Gang Xiong
- Department of General Surgery, Dazhou Central Hospital, Dazhou, Sichuan 635000, P.R. China
| | - Jun Zhang
- Department of General Surgery, Dazhou Central Hospital, Dazhou, Sichuan 635000, P.R. China
| | - Yichao Zhang
- Department of General Surgery, Dazhou Central Hospital, Dazhou, Sichuan 635000, P.R. China
| | - Xiao Pang
- Department of General Surgery, Dazhou Central Hospital, Dazhou, Sichuan 635000, P.R. China
| | - Biao Wang
- Department of General Surgery, Dazhou Central Hospital, Dazhou, Sichuan 635000, P.R. China
| | - Yongchuan Zhang
- Department of General Surgery, Dazhou Central Hospital, Dazhou, Sichuan 635000, P.R. China
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12
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Wang X, Song Z, Hu B, Chen Z, Chen F, Cao C. MicroRNA‑642a‑5p inhibits colon cancer cell migration and invasion by targeting collagen type I α1. Oncol Rep 2021; 45:933-944. [PMID: 33650641 PMCID: PMC7859924 DOI: 10.3892/or.2020.7905] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 11/20/2020] [Indexed: 12/28/2022] Open
Abstract
The aim of the present study was to explore the mechanism by which microRNA (miR)‑642a‑5p regulates the migration and invasion of colon cancer cells via collagen type I α1 (COL1A1). The characteristics of miR‑642a‑5p and COL1A1 were analysed through bioinformatics. Cancer and normal tissues were collected from patients with colon cancer. miR‑642a‑5p‑ and COL1A1‑overexpressing cell lines were constructed by transfection. A dual‑luciferase reporter assay was used to verify the targeting of COL1A1 by miR‑642a‑5p. Cell Counting Kit‑8, wound healing and Transwell assays were used to detect cell viability, migration and invasion, respectively. Protein and mRNA expression levels were examined by western blotting and reverse transcription‑quantitative PCR, respectively. The results revealed that miR‑642a‑5p expression was significantly upregulated and COL1A1 expression was downregulated in patients with colon cancer. Low levels of miR‑642a‑5p and high levels of COL1A1 were associated with a poor prognosis in patients with colon cancer. miR‑642a‑5p directly targeted the 3'‑untranslated region of COL1A1 and inhibited COL1A1 expression. Overexpression of miR‑642a‑5p inhibited cell viability, migration, invasion and epithelial mesenchymal transition. Overexpression of COL1A1 promoted cell viability, migration, invasion and EMT, and partially reversed the inhibitory effects of miR‑642a‑5p on colon cancer cells. In conclusion, miR‑642a‑5p inhibited colon cancer cell migration, invasion and EMT by regulating COL1A1.
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Affiliation(s)
- Xiaoguang Wang
- Department of Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China
| | - Zhengwei Song
- Department of Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China
| | - Biwen Hu
- Department of Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China
| | - Zhenwei Chen
- Department of Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China
| | - Fei Chen
- Department of Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China
| | - Chenxi Cao
- Department of Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China
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MicroRNA signature in classical Hodgkin lymphoma. J Appl Genet 2021; 62:281-288. [PMID: 33544339 PMCID: PMC8032569 DOI: 10.1007/s13353-021-00614-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 12/30/2020] [Accepted: 01/11/2021] [Indexed: 12/11/2022]
Abstract
Classical Hodgkin lymphoma (cHL) is one of the most prevalent lymphomas with a unique cell composition compared to other lymphoma entities. Rare, malignant Hodgkin and Reed-Sternberg (HRS) cells embedded with an extensive but ineffective immune infiltration were previously characterized by a large number of genetic and epigenetic alterations. Recently, microRNA profiling studies highlighted the importance of small non-coding RNA in cHL. This review summarizes available literature data and provides a detailed comparison of four studies where cHL cell lines and microdissected HRS cells were used. Several microRNAs were found to be consistently up- (let-7-f, mir-9, mir-21, mir-23a, mir-27a, mir-155, and mir-196a) or downregulated (mir-138 and mir-150) in cHL. These deregulated microRNAs are involved in the processes crucial for cHL pathogenesis, such as impaired B cell development (mir-9, mir-150, and mir-155), NFκB hyperactivation (mir-155 and mir-196a), and immune evasion (mir-138). Therefore, the deregulation of microRNA expression can be considered a complementary mechanism to genetic alterations promoting lymphomagenesis. Moreover, the expression of let-7f, mir-9 and mir-27a is specific for cHL and can serve as a biomarker to distinguish this lymphoma from other B cell lymphomas. However, additional in-depth and high throughput analysis of microRNA expression in HRS cells is necessary to decipher the complete picture of microRNA in cHL.
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Peripheral Blood Cells from Patients with Hodgkin's and Diffuse Large B Cell Lymphomas May Be a Better Source of Candidate Diagnostic miRNAs Than Circulating miRNAs. BIOMED RESEARCH INTERNATIONAL 2021; 2021:3212878. [PMID: 33628777 PMCID: PMC7880712 DOI: 10.1155/2021/3212878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 01/08/2021] [Accepted: 01/21/2021] [Indexed: 11/18/2022]
Abstract
Hodgkin lymphoma (HL) and diffuse large B cell lymphoma (DLBCL) represent 15% and 20%, respectively, of all lymphoma types. The aim of this study was to identify and compare circulating serum miRNA (c-miRNA) and peripheral whole blood miRNA (wb-miRNA) profiles in patients with these lymphomas. Serum samples (20 HL, 21 DLBCL, and 30 healthy controls) and whole blood samples (21 HL, 17 DLBCL patients, and 30 healthy controls) were collected at the time of diagnosis. Serum and whole blood were also collected from 18 HL/17 DLBCL and eight HL/nine DLBCL patients, respectively, after treatment. Pairwise comparisons identified 125 c-miRNAs (adjusted P value < 0.05) showing significant dysregulation between 30 healthy controls and patients; of these, 47 and 55 differentiated controls from pretherapeutic HL and DLBCL patients, respectively. In addition, 60 and 16 c-miRNAs differentiated controls from posttherapeutic HL and DLBCL, respectively. Pairwise comparisons identified 292 wb-miRNAs (adjusted P value < 0.05) showing significant dysregulation between 30 controls and patients; of these, 103 and 169 differentiated controls from pretherapeutic HL and DLBCL, respectively, and 142 and 151 wb-miRNAs differentiated controls from posttherapeutic HL and DLBCL, respectively. Thus, lymphoma-associated miRNAs may be a better source of noninvasive candidate biomarkers than miRNAs in serum. It is unclear whether miRNA alterations in lymphoma cells are similar to those observed in white blood cells.
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15
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Identification of miR-320 family members as potential diagnostic and prognostic biomarkers in myelodysplastic syndromes. Sci Rep 2021; 11:183. [PMID: 33420276 PMCID: PMC7794569 DOI: 10.1038/s41598-020-80571-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 12/23/2020] [Indexed: 12/15/2022] Open
Abstract
Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and the abnormal differentiation of hematopoietic stem cells. An increasing number of researches have demonstrated that microRNAs play crucial roles in the pathogenesis of myelodysplastic syndromes. Herein, we aimed to identify novel potential microRNAs bound up with the diagnosis and prognosis of MDS. MiRNA microarray analysis was used to screen deregulated microRNAs in the bone marrow of MDS patients. qRT-PCR was employed to confirm the microarray results. All members of miR-320 family (miR-320a, miR-320b, miR-320c, miR-320d, and miR-320e) were significantly increased in MDS patients compared to normal control. Although we found no correlation between miR-320 family and most clinical characteristics, high miR-320c and miR-320d expression seemed to be associated with high numbers of bone marrow (BM) blasts and worse karyotype. High expression of all the members of the miR-320 family seemed to be associated with a high prognostic score based on International Prognostic Scoring System (IPSS). The areas under the miR-320 family member ROC curves were 0.9037 (P < 0.0001), 0.7515 (P = 0.0002), 0.9647 (P < 0.0001), 0.8064 (P < 0.0001) and 0.9019 (P < 0.0001). Regarding Kaplan-Meier analysis, high miR-320c and miR-320d expression were related to shorter overall survival (OS). Moreover, multivariate analysis revealed the independent prognostic value of miR-320d for OS in MDS. The expression of miR-320 family members was up-regulated in MDS, and miR-320 family members could serve as candidate diagnostic biomarkers for MDS. High expression of miR-320d was an independent prognostic factor for OS in MDS.
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Morales-Martinez M, Lichtenstein A, Vega MI. Function of Deptor and its roles in hematological malignancies. Aging (Albany NY) 2021; 13:1528-1564. [PMID: 33412518 PMCID: PMC7834987 DOI: 10.18632/aging.202462] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 12/10/2020] [Indexed: 12/12/2022]
Abstract
Deptor is a protein that interacts with mTOR and that belongs to the mTORC1 and mTORC2 complexes. Deptor is capable of inhibiting the kinase activity of mTOR. It is well known that the mTOR pathway is involved in various signaling pathways that are involved with various biological processes such as cell growth, apoptosis, autophagy, and the ER stress response. Therefore, Deptor, being a natural inhibitor of mTOR, has become very important in its study. Because of this, it is important to research its role regarding the development and progression of human malignancies, especially in hematologic malignancies. Due to its variation in expression in cancer, it has been suggested that Deptor can act as an oncogene or tumor suppressor depending on the cellular or tissue context. This review discusses recent advances in its transcriptional and post-transcriptional regulation of Deptor. As well as the advances regarding the activities of Deptor in hematological malignancies, its possible role as a biomarker, and its possible clinical relevance in these malignancies.
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Affiliation(s)
- Mario Morales-Martinez
- Molecular Signal Pathway in Cancer Laboratory, UIMEO, Oncology Hospital, Siglo XXI National Medical Center, IMSS, México City, México
| | - Alan Lichtenstein
- Department of Medicine, Hematology-Oncology Division, Greater Los Angeles VA Healthcare Center, UCLA Medical Center, Jonsson Comprehensive Cancer Center, Los Angeles, CA 90024, USA
| | - Mario I. Vega
- Molecular Signal Pathway in Cancer Laboratory, UIMEO, Oncology Hospital, Siglo XXI National Medical Center, IMSS, México City, México
- Department of Medicine, Hematology-Oncology Division, Greater Los Angeles VA Healthcare Center, UCLA Medical Center, Jonsson Comprehensive Cancer Center, Los Angeles, CA 90024, USA
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17
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Annese T, Tamma R, De Giorgis M, Ribatti D. microRNAs Biogenesis, Functions and Role in Tumor Angiogenesis. Front Oncol 2020; 10:581007. [PMID: 33330058 PMCID: PMC7729128 DOI: 10.3389/fonc.2020.581007] [Citation(s) in RCA: 155] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 10/27/2020] [Indexed: 12/19/2022] Open
Abstract
microRNAs (miRNAs) are small non-coding RNA molecules, evolutionary conserved. They target more than one mRNAs, thus influencing multiple molecular pathways, but also mRNAs may bind to a variety of miRNAs, either simultaneously or in a context-dependent manner. miRNAs biogenesis, including miRNA transcription, processing by Drosha and Dicer, transportation, RISC biding, and miRNA decay, are finely controlled in space and time. miRNAs are critical regulators in various biological processes, such as differentiation, proliferation, apoptosis, and development in both health and disease. Their dysregulation is involved in tumor initiation and progression. In tumors, they can act as onco-miRNAs or oncosuppressor-miRNA participating in distinct cellular pathways, and the same miRNA can perform both activities depending on the context. In tumor progression, the angiogenic switch is fundamental. miRNAs derived from tumor cells, endothelial cells, and cells of the surrounding microenvironment regulate tumor angiogenesis, acting as pro-angiomiR or anti-angiomiR. In this review, we described miRNA biogenesis and function, and we update the non-classical aspects of them. The most recent role in the nucleus, as transcriptional gene regulators and the different mechanisms by which they could be dysregulated, in tumor initiation and progression, are treated. In particular, we describe the role of miRNAs in sprouting angiogenesis, vessel co-option, and vasculogenic mimicry. The role of miRNAs in lymphoma angiogenesis is also discussed despite the scarcity of data. The information presented in this review reveals the need to do much more to discover the complete miRNA network regulating angiogenesis, not only using high-throughput computational analysis approaches but also morphological ones.
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Affiliation(s)
- Tiziana Annese
- Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Section of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy
| | - Roberto Tamma
- Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Section of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy
| | - Michelina De Giorgis
- Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Section of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy
| | - Domenico Ribatti
- Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Section of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy
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18
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Xu J, Zhang Y, Huang Y, Dong X, Xiang Z, Zou J, Wu L, Lu W. circEYA1 Functions as a Sponge of miR-582-3p to Suppress Cervical Adenocarcinoma Tumorigenesis via Upregulating CXCL14. MOLECULAR THERAPY-NUCLEIC ACIDS 2020; 22:1176-1190. [PMID: 33312754 PMCID: PMC7701031 DOI: 10.1016/j.omtn.2020.10.026] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Accepted: 10/19/2020] [Indexed: 12/20/2022]
Abstract
Circular RNAs (circRNAs) function as efficient microRNA (miRNA) sponges that regulate gene expression in the pathogenesis of many human malignancies. However, their roles in cervical adenocarcinoma remain largely unknown. In this study, we aimed to seek novel circRNAs that regulate cervical adenocarcinoma carcinogenesis and to explore their regulatory mechanisms as well as clinical significance. We identified that 24 circRNAs were differentially expressed in cervical adenocarcinoma tissues by RNA sequencing. Among them, circEYA1 was the most significantly downregulated circRNA in cervical adenocarcinoma. In cervical adenocarcinoma cells, circEYA1 overexpression led to suppression of cell viability and colony formation, promotion of apoptosis, and a decrease of the xenograft tumor growth. The mechanism underlying these observations is that circEYA1 functioned as a sponge of miR-582-3p and abrogated its suppression of CXCL14 expression. Consistently, miR-582-3p inhibition phenocopied the biological effects of circEYA1 overexpression in cervical adenocarcinoma cells. Moreover, miR-582-3p overexpression reversed the suppressive behaviors of circEYA1 in vitro and in vivo. In addition, the expression, correlation, and clinical diagnostic value of circEYA1/miR-582-3p/CXCL14 were confirmed in 198 clinical cervical tissue samples. In summary, our findings highlight a novel tumor suppressive role of circEYA1 in cervical adenocarcinoma tumorigenesis and may provide a potential diagnostic marker and therapeutic target for patients with cervical adenocarcinoma.
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Affiliation(s)
- Junfen Xu
- Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
| | - Yanan Zhang
- Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Yongjie Huang
- Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
| | - Xiaohui Dong
- Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Zhenzhen Xiang
- Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
| | - Jian Zou
- Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
| | - Luyao Wu
- Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
| | - Weiguo Lu
- Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.,Center of Uterine Cancer Diagnosis & Therapy of Zhejiang Province, Hangzhou 310006, China
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Liu Y, Li Q, Dai Y, Jiang T, Zhou Y. miR-532-3p Inhibits Proliferation and Promotes Apoptosis of Lymphoma Cells by Targeting β-Catenin. J Cancer 2020; 11:4762-4770. [PMID: 32626523 PMCID: PMC7330684 DOI: 10.7150/jca.45684] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 05/23/2020] [Indexed: 12/11/2022] Open
Abstract
Background: Dysregulated expression of miR-532-3p has been observed in several types of cancer and plays a key role in tumor progression and metastasis. In this study, we analyzed the role and molecular mechanism of miR-532-3p in lymphoma progression. Methods: The expression of miR-532-3p in lymphoma sample tissues was analyzed using the GEO database and in cell lines by quantitative reverse transcription (qRT)-PCR. The functions of miR-532-3p in lymphoma cell proliferation and apoptosis were analyzed by CCK-8 assay and Annexin V-FITC/propidium iodide staining, respectively. In vivo, the tumor weight and volume were measured. The target gene of miR-532-3p was predicted using miRanda software, and then luciferase, qRT-PCR, and western blot assays were performed to verify that β-catenin was the downstream target gene of miR-532-3p. Results: miR-532-3p was decreased in lymphoma tissues and cell lines. In vitro and in vivo experiments showed that overexpression of miR-532-3p inhibited lymphoma cell proliferation and promoted apoptosis. Mechanistic studies demonstrated that β-catenin was a functional target gene of miR-532-3p. Furthermore, we found that overexpression of β-catenin reversed the tumor-suppression activities caused by overexpression of miR-532-3p in lymphoma proliferation and apoptosis. Conclusion: This study demonstrates that miR-532-3p functions as a tumor inhibitor in lymphoma progression by targeting β-catenin, suggesting miR-532-3p/β-catenin as a new diagnosis marker or potential therapeutic target in lymphoma.
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Affiliation(s)
- Yan Liu
- Department of Oncology, Putuo Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 20062, China.,Department of Hematology, Yueyang Hospital of Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
| | - Qiuying Li
- Department of Oncology, Putuo Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 20062, China
| | - Yongzhou Dai
- Department of Oncology, Putuo Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 20062, China
| | - Tinghui Jiang
- Department of Oncology, Putuo Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 20062, China
| | - Yongming Zhou
- Department of Hematology, Yueyang Hospital of Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
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20
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Non-coding RNAs in drug resistance of head and neck cancers: A review. Biomed Pharmacother 2020; 127:110231. [PMID: 32428836 DOI: 10.1016/j.biopha.2020.110231] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 04/30/2020] [Accepted: 05/03/2020] [Indexed: 02/06/2023] Open
Abstract
Head and neck cancer (HNC), which includes epithelial malignancies of the upper aerodigestive tract (oral cavity, oropharynx, pharynx, hypopharynx, larynx, and thyroid), are slowly but consistently increasing, while the overall survival rate remains unsatisfactory. Because of the multifunctional anatomical intricacies of the head and neck, disease progression and therapy-related side effects often severely affect the patient's appearance and self-image, as well as their ability to breathe, speak, and swallow. Patients with HNC require a multidisciplinary approach involving surgery, radiation therapy, and chemotherapeutics. Chemotherapy is an important part of the comprehensive treatment of tumors, especially advanced HNC, but drug resistance is the main cause of poor clinical efficacy. The most important determinant of this phenomenon is still largely unknown. Recent studies have shown that non-coding RNAs have a crucial role in HNC drug resistance. In addition, they can serve as biomarkers in the diagnosis, treatment, and prognosis of HNCs. In this review, we summarize the relationship between non-coding RNAs and drug resistance of HNC, and discuss their potential clinical application in overcoming HNC chemoresistance.
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21
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Li P, Cai JX, Han F, Wang J, Zhou JJ, Shen KW, Wang LH. Expression and significance of miR-654-5p and miR-376b-3p in patients with colon cancer. World J Gastrointest Oncol 2020; 12:492-502. [PMID: 32368326 PMCID: PMC7191333 DOI: 10.4251/wjgo.v12.i4.492] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 02/05/2020] [Accepted: 03/12/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The relationship between microRNAs, such as miR-654-5p and miR-376b-3p, and the prognosis of colon cancer has not been studied until now.
AIM To evaluate the expression levels of miR-654-5p and miR-376b-3p and their clinical significance in colon cancer.
METHODS RT-qPCR was performed to evaluate miR-654-5p and miR-376b-3p expression in 34 pairs of colon cancer and adjacent noncancerous tissues. Subsequently, the association of miR-654-5p and miR-376b-3p expression with clinical factors or the survival of patients suffering from colon cancer was determined by using The Cancer Genome Atlas.
RESULTS miR-654-5p was upregulated and miR-376b-3p was downregulated in colon cancer tissues compared with adjacent noncancerous tissues (P < 0.001). Increased miR-654-5p and decreased miR-376b-3p expression levels were significantly associated with metastasis and clinical stage. Moreover, a univariate analysis demonstrated that colon cancer patients with high miR-654-5p or low miR-376b-3p expression (P = 0.044 and 0.007, respectively) had a poor overall survival rate. A multivariate analysis identified high miR-654-5p expression and low miR-376b-3p expression as independent predictors of poor survival in colon cancer patients.
CONCLUSION Upregulated miR-654-5p and downregulated miR-376b-3p may be associated with tumour progression in colon cancer, and these microRNAs may serve as independent prognostic markers for colon cancer.
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Affiliation(s)
- Ping Li
- Department of Central Laboratory, Huaian Tumor Hospital & Huaian Hospital of Huaian City, Huaian 223200, Jiangsu Province, China
- Department of General Surgery, Huaian Tumor Hospital & Huaian Hospital of Huaian City, Huaian 223200, Jiangsu Province, China
| | - Jia-Xun Cai
- Department of Anorectal, Clinical Medical College of Yangzhou University and Northern Jiangsu People’s Hospital, Yangzhou 225001, Jiangsu Province, China
| | - Fei Han
- Clinical Medical College, Yangzhou University, Yangzhou 225009, Jiangsu Province, China
| | - Jie Wang
- Clinical Medical College, Yangzhou University, Yangzhou 225009, Jiangsu Province, China
| | - Jia-Jie Zhou
- Clinical Medical College, Yangzhou University, Yangzhou 225009, Jiangsu Province, China
| | - Kai-Wen Shen
- Clinical Medical College, Yangzhou University, Yangzhou 225009, Jiangsu Province, China
| | - Liu-Hua Wang
- Department of General Surgery, General Surgery Institute of Yangzhou, Northern Jiangsu Province Hospital, Clinical Medical College, Yangzhou University, Yangzhou 225001, Jiangsu Province, China
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Ectopic Expression of miR-532-3p Suppresses Bone Metastasis of Prostate Cancer Cells via Inactivating NF-κB Signaling. MOLECULAR THERAPY-ONCOLYTICS 2020; 17:267-277. [PMID: 32368615 PMCID: PMC7191128 DOI: 10.1016/j.omto.2020.03.024] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 03/27/2020] [Indexed: 11/23/2022]
Abstract
miR-532-3p is a widely documented microRNA (miRNA) involved in multifaceted processes of cancer tumorigenesis and metastasis. However, the clinical significance and biological functions of miR-532-3p in bone metastasis of prostate cancer (PCa) remain largely unknown. Herein, we report that miR-532-3p was downregulated in PCa tissues with bone metastasis, and downexpression of miR-532-3p was significantly associated with Gleason grade and serum prostate-specific antigen (PSA) levels and predicted poor bone metastasis-free survival in PCa patients. Upregulating miR-532-3p inhibited invasion and migration abilities of PCa cells in vitro, while silencing miR-532-3p yielded an opposite effect on invasion and migration abilities of PCa cells. Importantly, upregulating miR-532-3p repressed bone metastasis of PCa cells in vivo. Our results further demonstrated that overexpression of miR-532-3p inhibited activation of nuclear facto κB (NF-κB) signaling via simultaneously targeting tumor necrosis factor receptor-associated factor 1 (TRAF1), TRAF2, and TRAF4, which further promoted invasion, migration, and bone metastasis of PCa cells. Therefore, our findings reveal a novel mechanism contributing to the sustained activity of NF-κB signaling underlying the bone metastasis of PCa.
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Hernández-Walias FJ, Vázquez E, Pacheco Y, Rodríguez-Fernández JM, Pérez-Elías MJ, Dronda F, Casado JL, Moreno A, Hermida JM, Quereda C, Hernando A, Tejerina-Picado F, Asensi V, Galindo MJ, Leal M, Moreno S, Vallejo A. Risk, Diagnostic and Predictor Factors for Classical Hodgkin Lymphoma in HIV-1-Infected Individuals: Role of Plasma Exosome-Derived miR-20a and miR-21. J Clin Med 2020; 9:jcm9030760. [PMID: 32168859 PMCID: PMC7141191 DOI: 10.3390/jcm9030760] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 02/27/2020] [Accepted: 03/08/2020] [Indexed: 02/07/2023] Open
Abstract
The incidence of classical Hodgkin lymphoma (cHL) in the HIV-1 setting has increased 5–25-fold compared to that observed in the general population. This study aimed to determine whether selected micro RNAs (miRs) and other soluble biomarkers and cellular subsets are dysregulated in cHL and could be used as biomarkers. This was a retrospective and longitudinal matched case-control study of 111 Caucasian, HIV-1-infected adult individuals, including 37 individuals with cHL and 74 with no type of cancer. Immunovirological data, plasma exosome-derived miR-16, miR-20a, miR-21, miR-221, miR-223, miR-106a, miR-185, miR-23, miR-30d, miR-222, miR-146a and miR-324, plasma IL-6, sCD14, sCD27, sCD30, sIL-2R, TNFR1, and cell phenotyping of T and B lymphocytes and natural killer (NK) cells were analyzed. Before cHL diagnosis, miR-20a, miR-21, and sCD30 were higher in cHL (p = 0.008, p = 0.009 and p = 0.042, respectively), while miR-16 was down-regulated (p = 0.040). miR-20a and miR-21 were independently associated with cHL (p = 0.049 and p = 0.035, respectively). The combination of miR-20a and miR-21 showed a good AUC value of 0.832 with a moderate likelihood ratio positive (LR+) value of 5.6 and a slight likelihood ratio negative (LR−) value of 0.23. At cHL diagnosis, miR-20a, miR-21 and miR-324 were overexpressed in cHL (p = 0.005, p = 0.024, and p = 0.001, respectively), while miR-223, miR-16, miR-185 and miR-106a were down regulated (p = 0.042, p = 0.007, p = 0.006, and p = 0.002, respectively). In addition, sCD14, sCD27, sCD30 and IL2R levels were higher in these individuals (p = 0.038, p = 0.010, p = 0.030, p = 0.006, respectively). miR-20a was independently associated with cHL (p = 0.011). The diagnostic value of miR-20a showed good AUC value of 0.754 (p = 0.074) with a slight LR+ value of 2 and a slight LR− of 0.25. After chemotherapy, miR-20a was higher in those individuals who had an adverse outcome (p < 0.001), while sCD14 and sCD30 were higher (p < 0.001). A specific signature of miRs and cytokines associated with a subsequent cHL diagnosis was found in this study, especially miR-20a and miR-21. Also, another biomarker signature was found at cHL diagnosis, with a relevant discriminant disease value for miR-20a. Of note, miR-20a expression was higher in those individuals who had an adverse clinical outcome after chemotherapy.
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Affiliation(s)
- Francisco J. Hernández-Walias
- Laboratory of Immunovirology, Infectious Diseases Department, Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain; (F.J.H.-W.); (E.V.); (M.J.P.-E.); (F.D.); (J.L.C.); (A.M.); (J.M.H.); (C.Q.); (S.M.)
| | - Esther Vázquez
- Laboratory of Immunovirology, Infectious Diseases Department, Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain; (F.J.H.-W.); (E.V.); (M.J.P.-E.); (F.D.); (J.L.C.); (A.M.); (J.M.H.); (C.Q.); (S.M.)
| | - Yolanda Pacheco
- Biomedicine Institute of Seville (IBiS), University Hospital Virgen del Rocío, 41013 Seville, Spain; (Y.P.); (M.L.)
| | | | - María J. Pérez-Elías
- Laboratory of Immunovirology, Infectious Diseases Department, Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain; (F.J.H.-W.); (E.V.); (M.J.P.-E.); (F.D.); (J.L.C.); (A.M.); (J.M.H.); (C.Q.); (S.M.)
| | - Fernando Dronda
- Laboratory of Immunovirology, Infectious Diseases Department, Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain; (F.J.H.-W.); (E.V.); (M.J.P.-E.); (F.D.); (J.L.C.); (A.M.); (J.M.H.); (C.Q.); (S.M.)
| | - José L. Casado
- Laboratory of Immunovirology, Infectious Diseases Department, Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain; (F.J.H.-W.); (E.V.); (M.J.P.-E.); (F.D.); (J.L.C.); (A.M.); (J.M.H.); (C.Q.); (S.M.)
| | - Ana Moreno
- Laboratory of Immunovirology, Infectious Diseases Department, Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain; (F.J.H.-W.); (E.V.); (M.J.P.-E.); (F.D.); (J.L.C.); (A.M.); (J.M.H.); (C.Q.); (S.M.)
| | - José M. Hermida
- Laboratory of Immunovirology, Infectious Diseases Department, Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain; (F.J.H.-W.); (E.V.); (M.J.P.-E.); (F.D.); (J.L.C.); (A.M.); (J.M.H.); (C.Q.); (S.M.)
| | - Carmen Quereda
- Laboratory of Immunovirology, Infectious Diseases Department, Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain; (F.J.H.-W.); (E.V.); (M.J.P.-E.); (F.D.); (J.L.C.); (A.M.); (J.M.H.); (C.Q.); (S.M.)
| | - Asunción Hernando
- Department of Medicine, 12 de Octubre University Hospital, Universidad European University of Madrid, Instituto de Investigación Hospital 12 de Octubre (imas12), 28041 Madrid, Spain;
| | | | - Víctor Asensi
- Infectious Diseases Department, Central University Hospital of Asturias, University Medical School, 33011 Oviedo, Spain;
- Group of Translational Research in Infectious Diseases, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
| | | | - Manuel Leal
- Biomedicine Institute of Seville (IBiS), University Hospital Virgen del Rocío, 41013 Seville, Spain; (Y.P.); (M.L.)
- Department of Internal Medicine and Infectious Diseases, Viamed Hospital, Santa Ángela de la Cruz, 41014 Seville, Spain
| | - Santiago Moreno
- Laboratory of Immunovirology, Infectious Diseases Department, Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain; (F.J.H.-W.); (E.V.); (M.J.P.-E.); (F.D.); (J.L.C.); (A.M.); (J.M.H.); (C.Q.); (S.M.)
| | - Alejandro Vallejo
- Laboratory of Immunovirology, Infectious Diseases Department, Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain; (F.J.H.-W.); (E.V.); (M.J.P.-E.); (F.D.); (J.L.C.); (A.M.); (J.M.H.); (C.Q.); (S.M.)
- Correspondence:
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24
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Pan S, Ren F, Li L, Liu D, Li Y, Wang A, Li W, Dong Y, Guo W. MiR-328-3p inhibits cell proliferation and metastasis in colorectal cancer by targeting Girdin and inhibiting the PI3K/Akt signaling pathway. Exp Cell Res 2020; 390:111939. [PMID: 32142853 DOI: 10.1016/j.yexcr.2020.111939] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 02/13/2020] [Accepted: 03/01/2020] [Indexed: 12/24/2022]
Abstract
MiR-328-3p has been reported to be downregulated and serve as a tumor suppressor in several cancers. Previous studies only have reported the downregulation of miR-328-3p in CRC. However, the roles of miR-328-3p in CRC growth and metastasis were unknown. In this study, we demonstrated that miR-328-3p overexpression inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). The PI3K/Akt signaling pathway was also inactivated by miR-328-3p overexpression. MiR-328-3p knockdown showed the opposite effects. In addition, we confirmed that miR-328-3p directly bound to 3'UTR of Girdin and negatively regulated its expression. Girdin knockdown or treatment with PI3K inhibitor LY294002 blocked the effects of miR-328-3p inhibitor on cell proliferation, metastasis, and the PI3K/Akt signaling pathway. Moreover, pre-miR-328 decreased numbers of liver metastatic nodules, and reduced the levels of p-Akt, p-Girdin, and Girdin in metastatic tissues in liver. In conclusion, miR-328-3p may inhibit proliferation and metastasis of CRC cells by targeting Girdin and inactivating the PI3K/Akt signaling pathway. MiR-328-3p may be a novel target in cancer therapy.
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Affiliation(s)
- Shuang Pan
- Department of Physiology, School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China
| | - Fu Ren
- Biological Anthropology Institute, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China; Key Laboratory of Chinese Physical Characteristics Research of Liaoning Province, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China.
| | - Lei Li
- Department of Vascular Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116027, People's Republic of China.
| | - Dahua Liu
- Biological Anthropology Institute, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China; Key Laboratory of Chinese Physical Characteristics Research of Liaoning Province, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China
| | - Yao Li
- Department of Physiology, School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China
| | - Aimei Wang
- Department of Physiology, School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China
| | - Weihong Li
- Department of Physiology, School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China
| | - Yongyan Dong
- The First Clinical College, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People's Republic of China
| | - Wenjuan Guo
- School of Chemistry and Chemical Engineering, Tianjin Polytechnic University, Tianjin, 300387, People's Republic of China
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25
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Mazurek M, Litak J, Kamieniak P, Osuchowska I, Maciejewski R, Roliński J, Grajkowska W, Grochowski C. Micro RNA Molecules as Modulators of Treatment Resistance, Immune Checkpoints Controllers and Sensitive Biomarkers in Glioblastoma Multiforme. Int J Mol Sci 2020; 21:ijms21041507. [PMID: 32098401 PMCID: PMC7073212 DOI: 10.3390/ijms21041507] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 02/11/2020] [Accepted: 02/18/2020] [Indexed: 12/18/2022] Open
Abstract
Based on genome sequencing, it is estimated that over 90% of genes stored in human genetic material are transcribed, but only 3% of them contain the information needed for the production of body proteins. This group also includes micro RNAs representing about 1%–3% of the human genome. Recent studies confirmed the hypothesis that targeting molecules called Immune Checkpoint (IC) open new opportunities to take control over glioblastoma multiforme (GBM). Detection of markers that indicate the presence of the cancer occupies a very important place in modern oncology. This function can be performed by both the cancer cells themselves as well as their components and other substances detected in the patients’ bodies. Efforts have been made for many years to find a suitable marker useful in the diagnosis and monitoring of gliomas, including glioblastoma.
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Affiliation(s)
- Marek Mazurek
- Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland; (M.M.); (J.L.); (P.K.)
| | - Jakub Litak
- Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland; (M.M.); (J.L.); (P.K.)
- Department of Immunology, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland;
| | - Piotr Kamieniak
- Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland; (M.M.); (J.L.); (P.K.)
| | - Ida Osuchowska
- Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (I.O.); (R.M.)
| | - Ryszard Maciejewski
- Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (I.O.); (R.M.)
| | - Jacek Roliński
- Department of Immunology, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland;
| | - Wiesława Grajkowska
- Department of Oncopathology and Biostructure, „Pomnik-Centrum Zdrowia Dziecka” Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland;
| | - Cezary Grochowski
- Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; (I.O.); (R.M.)
- Laboratory of Virtual Man, Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland
- Correspondence:
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26
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Ren L, Zhang Z, Feng Y, Luo M, Hao Z. MicroRNA-876-5p represses the cell proliferation and invasion of colorectal cancer through suppressing YAP signalling via targeting RASAL2. Clin Exp Pharmacol Physiol 2020; 47:867-876. [PMID: 31990059 DOI: 10.1111/1440-1681.13264] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 01/22/2020] [Accepted: 01/23/2020] [Indexed: 12/18/2022]
Abstract
Aberrant expression of microRNA-876-5p (miR-876-5p) is implicated in the progression of multiple human cancers. However, the potential role of miR-876-5p in colorectal cancer remains poorly understood. The purpose of the current study was to investigate the potential role of miR-876-5p in colorectal cancer. miR-876-5p expression was significantly downregulated in colorectal cancer tissues and cell lines compared with normal controls. Gain-of-function assays revealed that miR-876-5p overexpression effectively repressed the malignant behaviours of colorectal cancer cells, including cell proliferation, colony formation, and invasion. Bioinformatics analysis predicted that RAS protein activator like 2 (RASAL2), a potential oncogene for colorectal cancer, is a putative miR-876-5p target gene. A luciferase reporter assay confirmed that miR-876-5p directly binds to the 3'-untranslated region (UTR) of RASAL2. Furthermore, both RASAL2 messenger RNA (mRNA) and protein expression were negatively modulated by miR-876-5p in colorectal cancer cells. Notably, there was an inverse correlation between miR-876-5p and RASAL2 expression in colorectal cancer tissue specimens. Moreover, miR-876-5p was involved in regulating the activation of Yes-associated protein (YAP) signalling through inhibiting RASAL2. However, the miR-876-5p-mediated antitumour effect on colorectal cancer cells was partially reversed by restoring RASAL2 expression. Notably, miR-876-5p upregulation impeded the tumour growth of colorectal cancer cells in vivo in nude mice. Overall, these results demonstrated that miR-876-5p exerts an antitumour function in colorectal cancer by targeting RASAL2 to suppress YAP signalling activation. These findings highlight the importance of the miR-876-5p/RASAL2/YAP axis in colorectal cancer progression and suggest that miR-876-5p is a potential therapeutic target for treating colorectal cancer.
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Affiliation(s)
- Li Ren
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhiyong Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yun Feng
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Miaosha Luo
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhiming Hao
- Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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27
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Ai C, Ma G, Deng Y, Zheng Q, Gen Y, Li W, Li Y, Zu L, Zhou Q. Nm23-H1 inhibits lung cancer bone-specific metastasis by upregulating miR-660-5p targeted SMARCA5. Thorac Cancer 2020; 11:640-650. [PMID: 32022430 PMCID: PMC7049508 DOI: 10.1111/1759-7714.13308] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 12/23/2019] [Accepted: 12/27/2019] [Indexed: 02/05/2023] Open
Abstract
Background Nm23‐H1 gene has been found to be an inhibitor of tumor metastasis in lung cancer. MicroRNAs (miRNAs) play key roles in tumor metastasis through multiple signaling pathways. This study explored whether the nm23‐H1 gene could inhibit invasion and metastasis of lung cancer cells by regulating miRNA‐660‐5p targets. Methods Quantitative real‐time PCR (qRT‐PCR) and western blots were used to measure the expression of nm23‐H1 and miR‐660‐5p of various human lung cancer cell lines. Cell counting kit‐8 (CCK‐8), wound‐healing and transwell assay were carried out to assess cell proliferation, migration and invasion of each cell line. Xenograft were applied to determine in vivo effects of miR‐660‐5p among nude mice. Luciferase assay and western blot were performed to determine the target gene of miR‐660‐5p. Results We found that high expression of nm23‐H1 correlated with decreased miRNA‐660‐5p expression. Inhibiting miR‐660‐5p suppressed lung cancer cells progression significantly in vitro, whereas overexpression of miR‐660‐5p facilitated tumor growth and bone metastasis in vivo. In addition, as the potential target gene of miR‐660‐5p, SMARCA5 overexpression in vitro suppressed tumor progression and osteolytic metastasis associated RANKL signaling, which is congruent with the effect of nm23‐H1 on the lung cancer cells. Conclusion Nm23‐H1 inhibits tumor progression and bone‐specific metastasis of lung cancer by regulating miR‐660‐5p/SMARCA5/RANKL axis, which indicates the related genes may serve as potential targets for the treatment of human lung cancer. Key points Significant findings of the study High expression of nm23‐H1 correlated with decreased miRNA‐660‐5p expression. Further, downregulation of miR‐660‐5p significantly suppressed the tumor progression and bone‐specific metastasis of lung cancer cells. What this study adds This is the first study to show an inverse association between nm23‐H1 and miR‐660‐5p, and confirm that nm23‐H1 inhibits tumor progression and bone‐specific metastasis of lung cancer by regulating miR‐660‐5p/SMARCA5/RANKL axis.
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Affiliation(s)
- Cheng Ai
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,Department of Cardiothoracic Surgery, Panzhihua Central Hospital of Sichuan, Panzhihua, China
| | - Guangzhi Ma
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yunfu Deng
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Qiangqiang Zheng
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yingcai Gen
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Wen Li
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yang Li
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Lingling Zu
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Qinghua Zhou
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.,Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
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28
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Bao J, Li X, Li Y, Huang C, Meng X, Li J. MicroRNA-141-5p Acts as a Tumor Suppressor via Targeting RAB32 in Chronic Myeloid Leukemia. Front Pharmacol 2020; 10:1545. [PMID: 32038235 PMCID: PMC6987442 DOI: 10.3389/fphar.2019.01545] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 11/29/2019] [Indexed: 12/11/2022] Open
Abstract
MicroRNA-141-5p (miR-141-5p), an important member of the miR-200 family, has been reported to be involved in cellular proliferation, migration, invasion, and drug resistance in different kinds of human malignant tumors. However, the role and function of miR-141-5p in chronic myeloid leukemia (CML) are unclear. In this current study, we found that the level of miR-141-5p was significantly decreased in peripheral blood cells from CML patients compared with normal blood cells and human leukemic cell line (K562 cells) compared with normal CD34+ cells, but was remarkably elevated in patients after treatment with nilotinib or imatinib. Suppression of miR-141-5p promoted K562 cell proliferation and migration in vitro. As expected, overexpression of miR-141-5p weakened K562 cell proliferation, migration, and promoted cell apoptosis. A xenograft model in nude mice showed that overexpression of miR-141-5p markedly suppressed tumor growth in vivo. Mechanistic studies suggested that RAB32 was the potential target of miR-141-5p, and silencing of RAB32 suppressed the proliferation and migration of K562 cells and promoted cell apoptosis. Taken together, our study demonstrates that miR-141-5p plays an important role in the activation of K562 cells in vitro and may act as a tumor suppressor via targeting RAB32 in the development of CML.
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Affiliation(s)
- Jing Bao
- Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, China.,Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Xiaofeng Li
- Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, China
| | - Yuhuan Li
- Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, China
| | - Cheng Huang
- Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, China
| | - Xiaoming Meng
- Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, China
| | - Jun Li
- Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, China
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29
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Li H, Tian X, Wang P, Huang M, Xu R, Nie T. MicroRNA-582-3p negatively regulates cell proliferation and cell cycle progression in acute myeloid leukemia by targeting cyclin B2. Cell Mol Biol Lett 2019; 24:66. [PMID: 31844417 PMCID: PMC6894134 DOI: 10.1186/s11658-019-0184-7] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 10/29/2019] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND MicroRNAs (miRNAs) function as post-transcriptional gene expression regulators. Some miRNAs, including the recently discovered miR-582-3p, have been implicated in leukemogenesis. This study aimed to reveal the biological function of miR-582-3p in acute myeloid leukemia (AML), which is one of the most frequently diagnosed hematological malignancies. METHODS The expression of miR-582-3p was determined using quantitative real-time PCR in blood samples from leukemia patients and in cell lines. Cell proliferation and cell cycle distribution were analyzed using the CCK-8, colony formation and flow cytometry assays. The target gene of miR-582-3p was verified using a dual-luciferase reporter assay. The G2/M phase arrest-related molecule contents were measured using western blotting analysis. RESULTS We found miR-582-3p was significantly downregulated in the blood samples from leukemia patients and in the cell lines. MiR-582-3p overexpression significantly impaired cell proliferation and induced G2/M cell cycle arrest in THP-1 cells. Furthermore, cyclin B2 (CCNB2) was confirmed as a target gene of miR-582-3p and found to be negatively regulated by miR-582-3p overexpression. More importantly, CCNB2 knockdown showed suppressive effects on cell proliferation and cell cycle progression similar to those caused by miR-582-3p overexpression. The inhibitory effects of miR-582-3p overexpression on cell proliferation and cell cycle progression were abrogated by CCNB2 transfection. CONCLUSION These findings indicate new functions and mechanisms for miR-582-3p in AML development. Further study could clarify if miR-582-3p and CCNB2 are potential therapeutic targets for the treatment of AML.
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MESH Headings
- Adolescent
- Adult
- Aged
- Case-Control Studies
- Cell Line, Tumor
- Cell Proliferation
- Computational Biology/methods
- Cyclin B2/antagonists & inhibitors
- Cyclin B2/genetics
- Cyclin B2/metabolism
- Female
- G2 Phase Cell Cycle Checkpoints/genetics
- Gene Expression Regulation, Leukemic
- Genes, Reporter
- Humans
- K562 Cells
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology
- Leukemia, Myeloid, Acute/genetics
- Leukemia, Myeloid, Acute/metabolism
- Leukemia, Myeloid, Acute/pathology
- Luciferases/genetics
- Luciferases/metabolism
- Male
- MicroRNAs/genetics
- MicroRNAs/metabolism
- Middle Aged
- RNA, Small Interfering/genetics
- RNA, Small Interfering/metabolism
- Signal Transduction
- THP-1 Cells
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Affiliation(s)
- Haixia Li
- Department of Integrated Chinese and Western Medicine, Hunan Children’s Hospital, Changsha, 410007 China
- Hunan University of Chinese Medicine, Changsha, 410208 China
| | - Xuefei Tian
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208 China
| | - Paoqiu Wang
- Department of Integrated Chinese and Western Medicine, Hunan Children’s Hospital, Changsha, 410007 China
| | - Mao Huang
- Department of Pediatric Rehabilitation, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, 050000 Hebei China
| | - Ronghua Xu
- Department of Hematology, The First Hospital of Hunan University of Chinese Medicine, 95 Shaoshan Middle Road, Changsha City, 410007 Hunan Province China
| | - Tian Nie
- Department of Hematology, The First Hospital of Hunan University of Chinese Medicine, 95 Shaoshan Middle Road, Changsha City, 410007 Hunan Province China
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Liu Q, Shi H, Yang J, Jiang N. Long Non-Coding RNA NEAT1 Promoted Hepatocellular Carcinoma Cell Proliferation and Reduced Apoptosis Through the Regulation of Let-7b-IGF-1R Axis. Onco Targets Ther 2019; 12:10401-10413. [PMID: 31819522 PMCID: PMC6890520 DOI: 10.2147/ott.s217763] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 10/15/2019] [Indexed: 12/28/2022] Open
Abstract
Background and aim Long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) is abnormally expressed in various human malignancies, including hepatocellular carcinoma (HCC). Let-7b is a miRNA with the effect of a tumor suppressor gene, and its expression level in various tumor tissues is lower than that in normal tissues. Studies have found that IGF-1R can be abnormally activated in the process of hepatocyte deterioration, and the expression level of IGF-1R in HCC is significantly up-regulated. The aim of this study was to investigate the functional mechanism of NEAT1/let-7b-IGF-1R axis in HCC. Methods The expressions of NEAT1 and microRNA (miR)-let-7b in HCC tissues and cell lines were quantified by quantitative real-time PCR (qRT-PCR). The effect of NEAT1 on tumor growth was observed in a mice model of transplanted hepatoma. The effects of down-regulation or up-regulation of NEAT1 expression in HCC cell lines were analysed from the perspectives of cell viability and apoptosis. The binding sites of NEAT1 and miR-let-7b were predicted by biological software. The expression of the miR-let-7b target molecules IGF-1R was detected by Western blotting. Results The results showed that the expressions of NEAT1 were significantly increased, while the expressions of miR-let-7b were decreased in the HCC tissues and cell lines. Additionally, it was found that the expressions of NEAT1 and miR-let-7b showed a negative correlation in HCC tissues. The mouse model experiments confirmed that the interference with NEAT1 expression inhibited the tumor growth. Meanwhile, the cell viability of HepG2/Huh7 cell lines was significantly decreased via the downregulation of NEAT1, whereas the corresponding rates of apoptosis were significantly increased. It was further proven that there was a certain negative regulatory mechanism between NEAT1 and miR-1et-7b, which was related to the expression of IGF-1R. Conclusion The over-expression of NEAT1 could promote the proliferation of HCC cells by inhibiting the expression of the miR-let-7b regulated by IGF-1R.
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Affiliation(s)
- Qin Liu
- Department of Gastroenterology, Weihai Municipal Hospital, Weihai, People's Republic of China
| | - Hexian Shi
- Department of Hepatobiliary Surgery, Heze Municipal Hospital, Heze, People's Republic of China
| | - Jianbo Yang
- Department of Oral Medicine, Weihai Stomatological Hospital, Weihai, People's Republic of China
| | - Ning Jiang
- Department of General Surgery, Shandong Provincial Third Hospital, Jinan, People's Republic of China
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MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC, WNT and AKT pathways. Oncogene 2019; 38:6035-6050. [PMID: 31278368 DOI: 10.1038/s41388-019-0860-0] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 01/28/2019] [Accepted: 04/16/2019] [Indexed: 01/06/2023]
Abstract
Ovarian cancer is the most lethal gynecological malignancy due to the silent nature on its early onset and the rapid acquisition of drug resistance. Histologically heterogeneous, it includes several subtypes with different mutational landscapes, hampering the development of effective targeted therapies. Non-coding RNAs are emerging as potential new therapeutic targets in cancer. To search for a microRNA signature related to ovarian carcinomas and study its potential as effective targeted therapy, we examined the expression of 768 miRNA in a large collection of tumor samples and found miR-654-5p to be infraexpressed in ovarian serous carcinomas, the most common and aggressive type. Restoration of miR-654-5p levels reduced tumor cell viability in vitro and in vivo and impaired sphere formation capacity and viability of ovarian cancer patient-derived ascitic cells ex vivo. CDCP1 and PLAGL2 oncogenes were found to be the most relevant direct miR-654-5p targets and both genes convey in a molecular signature associated with key cancer pathways relevant to ovarian tumorigenesis, such as MYC, WNT and AKT pathways. Together, we unveiled the tumor suppressor function of miR-654-5p, suggesting that its restoration or co-targeting of CDCP1 and PLAGL2 may be an effective therapeutic approach for ovarian cancer.
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RNA N6-methyladenosine modification participates in miR-660/E2F3 axis-mediated inhibition of cell proliferation in gastric cancer. Pathol Res Pract 2019; 215:152393. [PMID: 30914234 DOI: 10.1016/j.prp.2019.03.021] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 03/03/2019] [Accepted: 03/18/2019] [Indexed: 02/07/2023]
Abstract
Increasing evidence has shown that dysregulation of mircoRNA (miRNA) is linked to the development and progression of human cancer, including gastric cancer (GC). In the current study, by analysing the GEO database (GSE78091), we found that miR-660 was significantly downregulated in GC. Consistently, quantitative real-time PCR (qRT-PCR) results showed that miR-660 was dramatically decreased in GC tissues and cell lines. Importantly, low miR-660 expression was closely related to larger tumor size (P = 0.008), lymph node metastasis (P = 0.006), advanced TNM stage (P = 0.029), and poor outcome (P = 0.023). Ectopic expression of miR-660 inhibited proliferation of MGC-803 and AGS cells and induced apoptosis. Further mechanism experiments suggested that the well-known oncogene E2F3 (E2F transcription factor 3) was a downstream target of miR-660. Overexpression of miR-660 reduced the activity of E2F3 by directly binding to the 3221˜3226 region of E2F3 3`-UTR, and there was a strong negative correlation between the expression of miR-660 and E2F3 in GC tissues (r = - 0.648, P < 0.001). Furthermore, E2F3 overexpression abrogated the anti-proliferation effect of miR-660 in GC cell lines. Of note, we found an N6-methyladenosine (m6A) motif at the 3063˜3067 region of E2F3 3`-UTR, and this m6A-modified motif was required for the interaction between miR-660 and E2F3 3`-UTR. Collectively, our findings reveal the compelling role of m6A in GC and highlight the regulatory function of the miR-660/E2F3 pathway in GC progression.
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Huang S, Zou C, Tang Y, Wa Q, Peng X, Chen X, Yang C, Ren D, Huang Y, Liao Z, Huang S, Zou X, Pan J. miR-582-3p and miR-582-5p Suppress Prostate Cancer Metastasis to Bone by Repressing TGF-β Signaling. MOLECULAR THERAPY. NUCLEIC ACIDS 2019; 16:91-104. [PMID: 30852380 PMCID: PMC6409413 DOI: 10.1016/j.omtn.2019.01.004] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/25/2018] [Revised: 01/08/2019] [Accepted: 01/08/2019] [Indexed: 02/03/2023]
Abstract
A number of studies have reported that aberrant expression of microRNAs (miRNAs) closely correlates with the bone metastasis of prostate cancer (PCa). However, clinical significance and functional roles of both strands of a single miRNA in bone metastasis of PCa remain undefined. Here, we reported that miR-582-3p and miR-582-5p expression were simultaneously reduced in bone metastatic PCa tissues compared with non-bone metastatic PCa tissues. Downexpression of miR-582-3p and miR-582-5p strongly and positively correlated with advanced clinicopathological characteristics and shorter bone metastasis-free survival in PCa patients. Upregulating miR-582-3p and miR-582-5p inhibited invasion and migration abilities of PCa cells in vitro, as well as repressed bone metastasis in vivo. Our results further revealed that miR-582-3p and miR-582-5p attenuated bone metastasis of PCa via inhibiting transforming growth factor β (TGF-β) signaling by simultaneously targeting several components of TGF-β signaling, including SMAD2, SMAD4, TGF-β receptor I (TGFBRI), and TGFBRII. Moreover, deletion contributes to miR-582-3p and miR-582-5p downexpression in PCa tissues. Finally, clinical negative correlations of miR-582-3p and miR-582-5p with SMAD2, SMAD4, TGFBRI, and TGFBRII were demonstrated in PCa tissues. Thus, our findings explore a novel tumor-suppressive miRNA with its both strands implicated in bone metastasis of PCa, suggesting its potential therapeutic value in treatment of PCa bone metastasis.
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Affiliation(s)
- Shuai Huang
- Department of Orthopaedic Surgery, The Second Affiliated Hospital of Guangzhou Medical University, 510260 Guangzhou, China; Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China; Department of Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, 510080 Guangzhou, China.
| | - Changye Zou
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China; Department of Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, 510080 Guangzhou, China
| | - Yubo Tang
- Department of Pharmacy, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China
| | - Qingde Wa
- Department of Orthopaedic Surgery, The Affiliated Hospital of Zunyi Medical College, 563003 Zunyi, China
| | - Xinsheng Peng
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China; Department of Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, 510080 Guangzhou, China
| | - Xiao Chen
- Department of Pharmacy, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China
| | - Chunxiao Yang
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Dong Ren
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China; Department of Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, 510080 Guangzhou, China
| | - Yan Huang
- Department of Orthopaedic Surgery, The Second Affiliated Hospital of Guangzhou Medical University, 510260 Guangzhou, China
| | - Zhuangwen Liao
- Department of Orthopaedic Surgery, The Second Affiliated Hospital of Guangzhou Medical University, 510260 Guangzhou, China
| | - Sheng Huang
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Nanchang University, 330006 Nanchang, China
| | - Xuenong Zou
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China; Department of Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, 510080 Guangzhou, China.
| | - Jincheng Pan
- Department of Urology Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, China.
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Siriwardhana C, Khadka VS, Chen JJ, Deng Y. Development of a miRNA-seq based prognostic signature in lung adenocarcinoma. BMC Cancer 2019; 19:34. [PMID: 30621620 PMCID: PMC6325795 DOI: 10.1186/s12885-018-5206-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 12/10/2018] [Indexed: 12/29/2022] Open
Abstract
Background We utilized miRNAs expression and clinical data to develop a prognostic signature for patients with lung adenocarcinoma, with respect to their overall survival, to identify high-risk subjects based on their miRNA genomic profile. Methods MiRNA expressions based on miRNA sequencing and clinical data of lung adenocarcinoma patients (n = 479) from the Cancer Genome Atlas were randomly partitioned into non-overlapping Model (n = 320) and Test (n = 159) sets, respectively, for model estimation and validation. Results Among the ten miRNAs identified using the univariate Cox analysis, six from miR-8, miR-181, miR-326, miR-375, miR-99a, and miR-10, families showed improvement of the overall survival chance, while two miRNAs from miR-582 and miR-584 families showed a worsening of survival chances. The final prognostic signature was developed with five miRNAs—miR-375, miR-582-3p, miR-326, miR-181c-5p, and miR-99a-5p—utilizing a stepwise variable selection procedure. Using the KEGG pathway analysis, we found potential evidence supporting their significance in multiple cancer pathways, including non-small cell lung cancer. We defined two risk groups with a score calculated using the Cox regression coefficients. The five-year survival rates for the low-risk group was approximately 48.76% (95% CI = (36.15, 63.93)); however, it was as low as 7.50% (95% CI = (2.34, 24.01)) for the high-risk group. Furthermore, we demonstrated the effect of the genomic profile using the miRNA signature, quantifying survival rates for hypothetical subjects in different pathological stages of cancer. Conclusions The proposed prognostic signature can be used as a reliable tool for identifying high-risk subjects regarding survival based on their miRNA genomic profile. Electronic supplementary material The online version of this article (10.1186/s12885-018-5206-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Chathura Siriwardhana
- Bioinformatics and Biostatistics Cores, Department of Complementary and Integrative Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, HI, 96813, USA.
| | - Vedbar S Khadka
- Bioinformatics and Biostatistics Cores, Department of Complementary and Integrative Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, HI, 96813, USA
| | - John J Chen
- Bioinformatics and Biostatistics Cores, Department of Complementary and Integrative Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, HI, 96813, USA
| | - Youping Deng
- Bioinformatics and Biostatistics Cores, Department of Complementary and Integrative Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, HI, 96813, USA.
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Giunti L, Da Ros M, De Gregorio V, Magi A, Landini S, Mazzinghi B, Buccoliero AM, Genitori L, Giglio S, Sardi I. A microRNA profile of pediatric glioblastoma: The role of NUCKS1 upregulation. Mol Clin Oncol 2019; 10:331-338. [PMID: 30847170 PMCID: PMC6388501 DOI: 10.3892/mco.2019.1795] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 12/10/2018] [Indexed: 12/16/2022] Open
Abstract
MicroRNAs (miRNAs/miRs) are a novel class of gene regulators that may be involved in tumor chemoresistance. Recently, specific miRNA expression profiles have been identified in adult glioblastoma (aGBM), but there are only limited data available on the role of miRNAs in pediatric GBM (pGBM). In the present study, the expression profile of miRNAs was examined in seven pGBMs and three human GBM cell lines (U87MG, A172 and T98G), compared with a non-tumoral pool of pediatric cerebral cortex samples by microarray analysis. A set of differentially expressed miRNAs was identified, including miR-490, miR-876-3p, miR-876-5p, miR-448 and miR-137 (downregulated), as well as miR-501-3p (upregulated). Through bioinformatics analysis, a series of target genes was predicted. In addition, similar gene expression patterns in pGBMs and cell lines was confirmed. Of note, drug resistant T98G cells had upregulated nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) expression, a protein overexpressed in many tumors that serves an important role in cell proliferation and progression. On the basis of the present preliminary report, it could be intriguing to further investigate the relationship between each of the identified differentially expressed miRNAs and NUCKS1, in order to clarify their involvement in the multi-drug resistance mechanism of pGBMs.
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Affiliation(s)
- Laura Giunti
- Medical Genetics Unit, Meyer Children's University Hospital, I-50139 Florence, Italy
| | - Martina Da Ros
- Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children's University Hospital, I-50139 Florence, Italy
| | - Veronica De Gregorio
- Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children's University Hospital, I-50139 Florence, Italy
| | - Alberto Magi
- Department of Experimental and Clinical Medicine, University of Florence, I-50139 Florence, Italy
| | - Samuela Landini
- Medical Genetics Unit, Department of Clinical and Experimental Biomedical Sciences 'Mario Serio', University of Florence, I-50139 Florence, Italy
| | - Benedetta Mazzinghi
- Nephrology and Dialysis Unit, Meyer Children's University Hospital, I-50139 Florence, Italy
| | | | - Lorenzo Genitori
- Neurosurgery Unit, Meyer Children's University Hospital, I-50139 Florence, Italy
| | - Sabrina Giglio
- Medical Genetics Unit, Meyer Children's University Hospital, I-50139 Florence, Italy.,Medical Genetics Unit, Department of Clinical and Experimental Biomedical Sciences 'Mario Serio', University of Florence, I-50139 Florence, Italy
| | - Iacopo Sardi
- Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children's University Hospital, I-50139 Florence, Italy
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Li S, Pu T, Xiao L, Gao H, Li L, Ye F, Liu Y, Bu H. Screening of Recurrence Related MicroRNA in Ductal Carcinoma In Situ and Functional Study of MicroRNA-654-5p. J Breast Cancer 2019; 22:52-66. [PMID: 30941233 PMCID: PMC6438835 DOI: 10.4048/jbc.2019.22.e4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 11/16/2018] [Indexed: 02/05/2023] Open
Abstract
Purpose Ductal carcinoma in situ (DCIS) contributes to 20%–30% of newly diagnosed cases of breast cancer in China. Although the breast cancer-specific mortality of DCIS is extremely low, a small proportion of DCIS patients still show relapse or metastasis, leading to poor prognosis. Little is known about the molecular mechanism for DCIS metastasis, partly due to the limited number of poor prognosis patients. This study analyzed the clinicopathological features and screened key microRNAs (miRNAs) contributing to local or distant recurrence. Methods The clinicopathological features of DCIS were evaluated and survival analysis were performed to clarify risk factors associated with poor prognosis. Using miRNA arrays and real-time quantitative polymerase chain reaction (RT-qPCR) on DCIS formalin-fixed and paraffin-embedded samples with or without microinvasion with different clinical outcomes, potential DCIS metastasis-related miRNAs were screened out and further validated. The influence of one identified miRNA, miRNA-654-5p, on DCIS progression was analyzed. Results Poor prognosis was significantly associated with larger tumor size and higher lymph node metastasis rate (both p < 0.05). Both were independent prognostic factors for DCIS. According to RT-qPCR results, distinct miRNA expression profiles were identified between DCIS and DCIS with microinvasion (DCIS-Mi) patients. In the DCIS panel, miRNA-654-5p was significantly upregulated in the patients with poor prognosis. In vitro, miRNA-654-5p promoted MDA-MB-231 cell mobility in healing tests and metastasis in the Transwell study. Conclusion The panel of high-risk miRNAs in DCIS and DCIS-Mi differs markedly. miRNA-654-5p is significantly upregulated DCIS patients having poor prognosis and may be essential for local and distant recurrence in DCIS.
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Affiliation(s)
- Shi Li
- Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Tianjie Pu
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.,Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Lin Xiao
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Hongwei Gao
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.,Breast Cancer Center, Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Chengdu, China
| | - Li Li
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.,Breast Cancer Center, Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Chengdu, China
| | - Feng Ye
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.,Breast Cancer Center, Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Chengdu, China
| | - Yueping Liu
- Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Hong Bu
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.,Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.,Breast Cancer Center, Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Chengdu, China
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Wang J, Yin K, Lv X, Yang Q, Shao M, Liu X, Sun H. MicroRNA-24-3p regulates Hodgkin's lymphoma cell proliferation, migration and invasion by targeting DEDD. Oncol Lett 2018; 17:365-371. [PMID: 30655776 PMCID: PMC6313197 DOI: 10.3892/ol.2018.9599] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 10/09/2018] [Indexed: 01/07/2023] Open
Abstract
Hodgkin's lymphoma (HL) is a common hematologic tumor, and the incidence is increasing. At present, it is considered that miRNAs are closely related to HL. Substantial attention has been paid to the effects of miRNA on the pathophysiological process of HL. This study was focused on the potential role of miR-24-3p in HL by targeting DEDD. The reverse transcription-quantitative PCR (RT-qPCR) results demonstrated that miR-24-3p expression was highly elevated and DEDD expression reduced inversely in HL tissues compared to adjacent tissues. According to the results of CKK-8 assays, miR-24-3p was able to accelerate HL cell proliferation. In addition, the results of the Transwell assays also indicated that miR-24-3p promoted the invasion and migration abilities of HL cells. Moreover, the results demonstrated that miR-24-3p inhibited DEDD expression. Hence, the present study revealed that miR-24-3p could accelerate HL development through inhibiting DEDD.
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Affiliation(s)
- Jing Wang
- Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Kai Yin
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Xianping Lv
- Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Qiankun Yang
- Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Ming Shao
- Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Xin Liu
- Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Hui Sun
- Department of Hematopathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
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Carvalho de Oliveira J, Molinari Roberto G, Baroni M, Bezerra Salomão K, Alejandra Pezuk J, Sol Brassesco M. MiRNA Dysregulation in Childhood Hematological Cancer. Int J Mol Sci 2018; 19:ijms19092688. [PMID: 30201877 PMCID: PMC6165337 DOI: 10.3390/ijms19092688] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 09/03/2018] [Accepted: 09/08/2018] [Indexed: 12/14/2022] Open
Abstract
For decades, cancer biology focused largely on the protein-encoding genes that have clear roles in tumor development or progression: cell-cycle control, apoptotic evasion, genome instability, drug resistance, or signaling pathways that stimulate growth, angiogenesis, or metastasis. MicroRNAs (miRNAs), however, represent one of the more abundant classes of cell modulators in multicellular organisms and largely contribute to regulating gene expression. Many of the ~2500 miRNAs discovered to date in humans regulate vital biological processes, and their aberrant expression results in pathological and malignant outcomes. In this review, we highlight what has been learned about the roles of miRNAs in some of the most common human pediatric leukemias and lymphomas, along with their value as diagnostic/prognostic factors.
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Affiliation(s)
| | - Gabriela Molinari Roberto
- Department of Pediatrics, Ribeirão Preto School of Medicine, University of São Paulo, 14049-900 Ribeirão Preto, Brazil.
| | - Mirella Baroni
- Department of Pediatrics, Ribeirão Preto School of Medicine, University of São Paulo, 14049-900 Ribeirão Preto, Brazil.
| | - Karina Bezerra Salomão
- Department of Pediatrics, Ribeirão Preto School of Medicine, University of São Paulo, 14049-900 Ribeirão Preto, Brazil.
| | - Julia Alejandra Pezuk
- Programa de Pós-graduação em Farmácia, Anhanguera University of São Paulo, UNIAN/SP, 05145-200 São Paulo, Brazil.
| | - María Sol Brassesco
- Departamento de Biologia, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo, 14040-901 Ribeirão Preto, Brazil.
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Dong Y, Zheng Y, Wang C, Ding X, Du Y, Liu L, Zhang W, Zhang W, Zhong Y, Wu Y, Song X. MiR-876-5p modulates head and neck squamous cell carcinoma metastasis and invasion by targeting vimentin. Cancer Cell Int 2018; 18:121. [PMID: 30181714 PMCID: PMC6114268 DOI: 10.1186/s12935-018-0619-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 08/14/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Local or distant metastasis remains the main course of death in head and neck squamous cell carcinoma (HNSCC) patients. MicroRNAs (miRNAs) have been implicated in metastasis of HNSCC, but the mechanisms of their action are mainly undocumented. Through public head and neck cancer miRNA expression datasets, we found that miR-876-5p was a novel potential tumor suppressor targeting HNSCC metastasis. METHODS Clinical significance and mechanism of miR-876-5P was systematically analyzed in HNSCC. Quantitative RT-PCR was used to evaluate miR-876-5p levels in HNSCC cell lines and in 20 pairs of HNSCC with associated regional nodal metastases and HNSCC without metastatic primary tumors. Scratch and invasion assays were evaluated to determine the role of miR-876-5p in the regulation of HNSCC cell migration and invasion, respectively. Western blotting was used to investigate the mechanism by which miR-876-5p suppresses HNSCC cell invasion and migration. Luciferase assays were performed to assess miR-876-5p binding to the vimentin gene. The animal model was used to support the in vitro experimental findings. RESULTS MiR-876-5p mimics inhibited HNSCC cell migration and invasion. Vimentin protein and mRNA levels were decreased in the miR-876-5p mimics group but increased in the miR-876-5p inhibitors group, which demonstrated that miR-876-5p inhibits vimentin expression in HNSCC cells. By directly targeting the vimentin 3'-UTR, we used dual-luciferase reporter assays to verify that vimentin is a functional downstream target of miR-876-5p. Importantly, increased vimentin expression promoted cell migration and invasion, and co-transfection with miR-876-5p mimics and vimentin restored cell aggressiveness to the original level. Moreover, miR-876-5p overexpression significantly downregulated vimentin expression level and inhibited the distal metastasis of HNSCC cells in vivo. CONCLUSIONS miR-876-5p, which functions as a tumor suppressor in HNSCC, inhibits metastasis by targeting vimentin and provides a novel therapeutic target for HNSCC treatment.
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Affiliation(s)
- Yibo Dong
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140, Hanzhong Road, Nanjing, 210029 China
- Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 136, Hanzhong Road, Nanjing, 210029 China
| | - Yang Zheng
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140, Hanzhong Road, Nanjing, 210029 China
- Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 136, Hanzhong Road, Nanjing, 210029 China
| | - Chundi Wang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140, Hanzhong Road, Nanjing, 210029 China
- Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 136, Hanzhong Road, Nanjing, 210029 China
| | - Xu Ding
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140, Hanzhong Road, Nanjing, 210029 China
- Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 136, Hanzhong Road, Nanjing, 210029 China
| | - Yifei Du
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140, Hanzhong Road, Nanjing, 210029 China
- Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 136, Hanzhong Road, Nanjing, 210029 China
| | - Laikui Liu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140, Hanzhong Road, Nanjing, 210029 China
| | - Wei Zhang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140, Hanzhong Road, Nanjing, 210029 China
| | - Wei Zhang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140, Hanzhong Road, Nanjing, 210029 China
- Department of Oral Pathology, Affiliated Hospital of Stomatology, Nanjing Medical University, 136, Hanzhong Road, Nanjing, 210029 China
| | - Yi Zhong
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140, Hanzhong Road, Nanjing, 210029 China
- Department of Oral Pathology, Affiliated Hospital of Stomatology, Nanjing Medical University, 136, Hanzhong Road, Nanjing, 210029 China
| | - Yunong Wu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140, Hanzhong Road, Nanjing, 210029 China
- Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 136, Hanzhong Road, Nanjing, 210029 China
| | - Xiaomeng Song
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140, Hanzhong Road, Nanjing, 210029 China
- Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 136, Hanzhong Road, Nanjing, 210029 China
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Bao L, Lv L, Feng J, Chen Y, Wang X, Han S, Zhao H. MiR-876-5p suppresses epithelial-mesenchymal transition of lung cancer by directly down-regulating bone morphogenetic protein 4. J Biosci 2018; 42:671-681. [PMID: 29229885 DOI: 10.1007/s12038-017-9722-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Lung cancer is the leading cause of cancer-related death throughout the world. We aimed to investigate the role of a novel microRNA-876-5p and its potential molecular target bone morphogenetic protein 4 (BMP-4), in the epithelial-mesenchymal transition (EMT) of lung cancer. Expressions of microRNA-876-5p and its potential target BMP-4 were analysed in lung cancer cells and patient tissues. Luciferase activity assay was conducted to verify direct targeting of microRNA- 876-5p to the 3'-UTR of BMP-4 mRNA. Migration, invasion capacities of lung cancer cells expressing microRNA-876-5p were analysed, and characteristics of lung cancer EMT protein markers were also evaluated. A xenograft tumour mouse model was established to address the roles of microRNA-876-5p and BMP-4 in lung cancer EMT in vivo. MicroRNA-876- 5p was decreased while BMP-4 was increased in lung cancer cells and tissues. MicroRNA-876-5p directly targeted 3'-UTR of BMP-4 mRNA to inhibit its expression. MicroRNA-876-5p expression significantly inhibited the migration, invasion and EMT of lung cancer cells in vitro, as well as metastasis in vivo, which required BMP-4 expression. MicroRNA-876-5p suppresses EMT of lung cancer by directly down-regulating BMP-4, both of which could serve as potential therapeutic targets in the treatment of lung cancer.
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Affiliation(s)
- Liang Bao
- Department of Respirology, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214002, Jiangsu Province, China
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Sang M, Meng L, Sang Y, Liu S, Ding P, Ju Y, Liu F, Gu L, Lian Y, Li J, Wu Y, Zhang X, Shan B. Circular RNA ciRS-7 accelerates ESCC progression through acting as a miR-876-5p sponge to enhance MAGE-A family expression. Cancer Lett 2018; 426:37-46. [DOI: 10.1016/j.canlet.2018.03.049] [Citation(s) in RCA: 109] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 03/21/2018] [Accepted: 03/29/2018] [Indexed: 01/18/2023]
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Yao S, Liu Y, Yao Z, Zhao Y, Wang H, Xu Y, Zhang J, Li J, Yang S. MicroRNA-376a regulates cell proliferation and apoptosis by targeting forkhead box protein P2 in lymphoma. Oncol Lett 2018; 16:3169-3176. [PMID: 30127911 DOI: 10.3892/ol.2018.9012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 11/29/2017] [Indexed: 02/05/2023] Open
Abstract
The present study aimed to investigate microRNA-376a (miR-376a) expression in lymphoma, and to investigate the effect of miR-376a on cell proliferation and apoptosis at cytological and molecular levels. The expression of miR-376a in lymphoma issue and cells was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR), the expression of forkhead box protein P2 (FOXP2) was detected by RT-qPCR and western blot analysis, and the effect of miR-376a on cell proliferation and apoptosis were studied by an MTT assay and flow cytometry, respectively. Additionally, the expression levels of cyclin D2, cyclin A, cyclin B, apoptosis-associated proteins B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected by western blot analysis. Furthermore, the target of miR-376a was predicted and clarified using a dual-luciferase reporter assay. The expression of miR-376a was downregulated and FOXP2 was upregulated in lymphoma tissues and cells. miR-376a overexpression inhibited lymphoma cell proliferation and induced apoptosis by regulating the expression levels of cyclin D2, cyclin A, Bax and Bcl-2. The dual-luciferase reporter assay demonstrated that FOXP2 was a target of miR-376a. miR-376a overexpression induced apoptosis by targeting FOXP2. Overexpression of miR-376a inhibited cell proliferation and induced apoptosis by targeting FOXP2 in lymphoma. Therefore, miR-376a and FOXP2 have the potential for use as biomarkers of lymphoma.
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Affiliation(s)
- Shuna Yao
- Section of Comprehensive Lymphoma, Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Yanyan Liu
- Section of Comprehensive Lymphoma, Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Zhihua Yao
- Section of Comprehensive Lymphoma, Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Yan Zhao
- Section of Comprehensive Lymphoma, Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Haiying Wang
- Section of Comprehensive Lymphoma, Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Yuanlin Xu
- Section of Comprehensive Lymphoma, Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Jiuyang Zhang
- Section of Comprehensive Lymphoma, Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Jing Li
- Section of Comprehensive Lymphoma, Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
| | - Shujun Yang
- Section of Comprehensive Lymphoma, Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
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Zhang P, Gao H, Li Q, Chen X, Wu X. Downregulation of microRNA‑660 inhibits cell proliferation and invasion in osteosarcoma by directly targeting forkhead box O1. Mol Med Rep 2018; 18:2433-2440. [PMID: 29901128 DOI: 10.3892/mmr.2018.9165] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Accepted: 05/22/2018] [Indexed: 11/05/2022] Open
Abstract
The abnormal expression of microRNAs (miRNAs/miRs) has been observed in osteosarcoma (OS), and these differently expressed miRNAs contribute to the occurrence and development of OS by regulating various biological behaviours. Therefore, a comprehensive understanding of the detailed roles of aberrantly expressed miRNAs in OS progression may be favourable to the identification of promising therapeutic strategies for the treatment of patients with this malignancy. The present study demonstrated that miR‑660‑5p (miR‑660) expression was significantly upregulated in OS tissues and cell lines compared with that in normal adjacent tissues and normal human osteoblast hFOB1.19, respectively. miR‑660 downregulation led to a significant decrease in the proliferation and invasion of OS cells. Forkhead box O1 (FOXO1) was predicted as a potential target of miR‑660. The subsequent luciferase reporter assay indicated that miR‑660 directly binds to the 3'‑untranslated region of FOXO1. Furthermore, miR‑660 inhibition increased the FOXO1 expression in OS cells at mRNA and protein levels. Moreover, FOXO1 was downregulated in OS tissues and this downregulation was negatively correlated with miR‑660 levels. Besides, rescue experiments demonstrated that FOXO1 knockdown abolished the effects of miR‑660 knockdown on OS cell proliferation and invasion. These results suggest that miR‑660 may serve oncogenic roles in OS by directly targeting FOXO1. Targeting miR‑660 may be an effective candidate for the treatment of patients with OS.
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Affiliation(s)
- Peng Zhang
- Department of Neurosurgery, Fujian Sanbo Funeng Brain Hospital, Fuzhou, Fujian 350001, P.R. China
| | - Haifeng Gao
- Department of Oncology, Dongying People's Hospital, Dongying, Shandong 257000, P.R. China
| | - Qing Li
- Department of Pathology, Dongying People's Hospital, Dongying, Shandong 257000, P.R. China
| | - Xinlei Chen
- Department of Orthopedics, Central Hospital of Zibo, Zibo, Shandong 255022, P.R. China
| | - Xifa Wu
- Department of Orthopedics, Central Hospital of Zibo, Zibo, Shandong 255022, P.R. China
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MicroRNA-876-5p inhibits epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by targeting BCL6 corepressor like 1. Biomed Pharmacother 2018; 103:645-652. [PMID: 29679906 DOI: 10.1016/j.biopha.2018.04.037] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Revised: 04/04/2018] [Accepted: 04/05/2018] [Indexed: 12/25/2022] Open
Abstract
Our previous study has reported that BCL6 corepressor like 1 (BCORL1) plays an oncogenic role in hepatocellular carcinoma (HCC) via promoting epithelial-mesenchymal transition (EMT) and tumor metastasis. However, the regulation of BCORL1 mediated by microRNAs (miRNAs) remains poorly known. The analysis of our clinical samples indicated that BCORL1 expression was markedly higher in HCC tissues than that in tumor-adjacent normal tissues. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed that high BCORL1 expression associated with high tumor grade, advanced tumor stage and poor survival of HCC patients. miR-875-5p expression was down-regulated and negatively correlated with BCORL1 mRNA expression in HCC tissues. Furthermore, miR-876-5p inversely regulated BCORL1 abundance in HCC cells by directly targeting the 3'-untranslated region (3'-UTR) of BCORL1. Ectopic expression of miR-876-5p suppressed cell migration and invasion in both HCCLM3 and MHCC97H cells. In accordance, miR-876-5p knockdown promoted the metastatic behaviors of Hep3B cells. Mechanistically, miR-876-5p suppressed the EMT progression of HCC cells. HCC tissues with high miR-876-5p level showed a higher E-cadherin staining compared to cases with low miR-876-5p level. Moreover, the repression of cell metastasis mediated by miR-876-5p was rescued by BCORL1 restoration in HCCLM3 cells. Notably, low miR-876-5p expression associated with venous infiltration, high tumor grade and advanced tumor stage. HCC patients with low miR-876-5p expression had a significant poorer overall survival and disease-free survival. To conclude, miR-876-5p inhibits EMT progression, migration and invasion of HCC cells by targeting BCORL1. Therefore, miR-876-5p/BCORL1 axis may represent as a novel therapeutic target for HCC treatment.
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Wu X, Wang F, Li Y, Wang X, Liu P, Zhang H, Ge Z, Zhang X, Gao C, Chen B. Evaluation of latent membrane protein 1 and microRNA-155 for the prognostic prediction of diffuse large B cell lymphoma. Oncol Lett 2018; 15:9725-9734. [PMID: 29844839 PMCID: PMC5958882 DOI: 10.3892/ol.2018.8560] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 03/16/2018] [Indexed: 12/23/2022] Open
Abstract
Diffuse large B cell lymphoma (DLBCL) has previously been demonstrated to contribute to the mortality of lymphoma with various aggressive features. The prognostic role of the biomarkers latent membrane protein (LMP) 1 and microRNA-(miR)-155 in DLBCL remain controversial. The present study primarily aimed to assess the effect of LMP1 and miR-155 on the survival of DLBCL patients, and additionally evaluate the clinical features to observe their influence on outcomes, compared with previous studies. Formalin-fixed and paraffin-embedded samples were collected from our center between May 2010 and December 2011. Microarray analysis, immunohistochemical analysis and reverse transcription-quantitative polymerase chain reaction were used to evaluate the expression of LMP1 and miR-155. The association between biomarkers or clinical features and patient outcomes was assessed using the log-rank statistical test, Cox proportional hazard model and Kaplan-Meier method. SPSS software was used to statistically analyze the data. A total of 82 patients were included in the present study. The results demonstrated that high expression of LMP1 and miR-155 may be associated with a poor progression-free survival rate, while a high International Prognostic Index score and high expression of LMP1 may be associated with a poor overall survival rate. These results indicated that LMP1 and miR-155 may be novel and reliable biomarkers for the prognostic prediction of lymphoma, and will potentially be analyzed in the future to evaluate patient prognosis.
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Affiliation(s)
- Xue Wu
- Department of Hematology (Key Department of Jiangsu Medicine), Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Fei Wang
- Department of Hematology (Key Department of Jiangsu Medicine), Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Yuan Li
- Department of Oncology, Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Xiyong Wang
- Department of Oncology, Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Ping Liu
- Department of Hematology (Key Department of Jiangsu Medicine), Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Haijun Zhang
- Department of Oncology, Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Zheng Ge
- Department of Hematology (Key Department of Jiangsu Medicine), Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Xiaoping Zhang
- Department of Hematology (Key Department of Jiangsu Medicine), Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Chong Gao
- Department of Hematology (Key Department of Jiangsu Medicine), Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Baoan Chen
- Department of Hematology (Key Department of Jiangsu Medicine), Medical School, The Affiliated Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
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MiR-876-5p acts as an inhibitor in hepatocellular carcinoma progression by targeting DNMT3A. Pathol Res Pract 2018; 214:1024-1030. [PMID: 29724530 DOI: 10.1016/j.prp.2018.04.012] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Revised: 04/04/2018] [Accepted: 04/17/2018] [Indexed: 12/21/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the biggest challenges that human beings faced with in 21st century. Previous researches have revealed that miRNAs can serve as regulators in various cancers. MiR-876-5p, a member of miRNA family, has been studied in lung cancer for its anti-oncogenic function. However, the exact function of it is not reported in HCC. Our study aims to find out the effects of miR-876-5p expression on HCC progression. Two HCC cells were chosen to do functional assays after miR-876-5p expression was detected in cell lines by qRT-PCR. HepG2 cell was transfected with miR-876-5p mimics, whereas LM3 cell was transfected with miR-876-5p inhibitors. Next, cell activities of these two indicated cells were analyzed by means of MTT assay, colony forming assay, transwell migration assay and western blot analysis. Consequently, we found that miR-876-5p could inhibit both cell proliferation and metastasis. Moreover, we found out a target gene (DNMT3A) of miR-876-5p by performing bioinformatics analysis, dual luciferase reporter assay and biotin-avidin pull-down assay. Finally, rescue assays were carried out in HepG2 cells. We found that DNMT3A could reverse miR-876-5p mimics-induced inhibition. Therefore, we concluded that miR-876-5p suppressed hepatocellular carcinoma progression by targeting DNMT3A.
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Paziewska A, Mikula M, Dabrowska M, Kulecka M, Goryca K, Antoniewicz A, Dobruch J, Borowka A, Rutkowski P, Ostrowski J. Candidate diagnostic miRNAs that can detect cancer in prostate biopsy. Prostate 2018; 78:178-185. [PMID: 29226351 DOI: 10.1002/pros.23427] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 08/30/2017] [Indexed: 12/30/2022]
Abstract
BACKGROUND While histopathological evaluation remains the gold standard for diagnosis of prostate cancer (PCa), sampling errors remain a frequent problem; therefore, use of tissue biomarkers that can distinguish between benign and malignant prostate disease is a potentially beneficial diagnostic strategy. METHODS Deep sequencing of the miRNA transcriptome of 14 benign prostatic hyperplasia (BPH) and 60 cancerous and non-cancerous prostate samples extracted from 34 cancer-bearing prostates removed by prostatectomy was performed; of the latter 60 samples, 16, 21, and 23 samples contained <10%, >30%, and no dysplastic cells, respectively. The predictive value of selected miRNAs was then tested by quantitative reverse-transcribed PCR (qRT-PCR), using two separate chemistries, Exiqon and Taqman, to evaluate the tissue samples obtained by prostatectomy. Validation experiments were also performed for a subset of miRNAs by qRT-PCR of 87 prostate core biopsies. RESULTS We identified 123 miRNAs significantly dysregulated in PCa (adjusted P-values <0.05); 110 and 13 miRNAs were dysregulated only in cancerous samples and non-cancerous samples extracted from cancer-bearing prostates, respectively, while 31 were dysregulated regardless of the dysplastic cell content of the studied specimens. The clinical utility of eight selected miRNAs was analyzed using the same sample set with two qRT-PCR chemistries. Measurable qRT-PCR signals were obtained for seven and six miRNAs using the Exiqon and Taqman chemistries, respectively, and expression levels of six and four of these miRNAs differed significantly between BPH and PCa samples, regardless of dysplastic cell content. Validation experiments on core biopsies using qRT-PCR confirmed differential expression between BPH and PCa of four miRNAs (miR-187-3p, miR-183-5p, miR-32-5p, and miR-141-5p) using the Exiqon and one miRNA (miR-187-3p) with the Taqman chemistry. CONCLUSIONS Our sequencing analyses identified several candidate diagnostic miRNAs and confirmed some which have previously been reported as diagnostic in prostate malignancy. The results of this study suggest also that some of selected miRNAs can differentiate between non-malignant and malignant prostates even when neoplastic cells are missing from the studied specimen.
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Affiliation(s)
- Agnieszka Paziewska
- Departmentof Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Michal Mikula
- Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Michalina Dabrowska
- Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Maria Kulecka
- Departmentof Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Krzysztof Goryca
- Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Artur Antoniewicz
- Department of Urology, Multidisciplinary Hospital Warsaw-Miedzylesie, Warsaw, Poland
| | - Jakub Dobruch
- Clinical Department of Urology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Andrzej Borowka
- Clinical Department of Urology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Piotr Rutkowski
- Department of Soft Tissue, Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Jerzy Ostrowski
- Departmentof Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
- Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
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Lu M, Wang C, Chen W, Mao C, Wang J. miR-654-5p Targets GRAP to Promote Proliferation, Metastasis, and Chemoresistance of Oral Squamous Cell Carcinoma Through Ras/MAPK Signaling. DNA Cell Biol 2018; 37:381-388. [PMID: 29364705 DOI: 10.1089/dna.2017.4095] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Oral squamous cell carcinoma (OSCC) is characterized by rapid local migration and invasion. This study was aimed at clarifying the effect of miR-654-5p on progression of OSCC. miR-654-5p promoted proliferation, metastasis, and chemoresistance of OSCC in vitro and in vivo. Consistently, miR-654-5p was upregulated in late-stage OSCC and was correlated with poor prognosis of OSCC patients. Furthermore, miR-654-5p was mechanistically verified to target Grb-2-related adaptor protein (GRAP), accompanied by the activation of Ras/MAPK signaling and the facilitation of epithelial-mesenchymal transition in OSCC cells. GRAP was downregulated in T1-2 stage versus T3-4 stage head and neck squamous cell carcinoma (HNSC) and was negatively correlated with tumor-node-metastases (TNM) stage in HNSC patients based on The Cancer Genome Atlas (TCGA) analysis. In addition, GRAP was positively correlated with good prognosis in HNSC patients. Our findings suggest that the miR-654-5p/GRAP/Ras/Erk signaling pathway in OSCC cells might contribute to the underlying mechanism through which miR-654-5p participates in the regulation of OSCC progression. miR-654-5p, as a potential biomarker for the clinical diagnosis and prognosis of OSCC, may be an effective anticancer target for the treatment of OSCC.
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Affiliation(s)
- Meng Lu
- Department of Oral Surgery, The Union Hospital of Fujian Medical University , Fuzhou, Fujian, P.R. China
| | - Chengyong Wang
- Department of Oral Surgery, The Union Hospital of Fujian Medical University , Fuzhou, Fujian, P.R. China
| | - Weihui Chen
- Department of Oral Surgery, The Union Hospital of Fujian Medical University , Fuzhou, Fujian, P.R. China
| | - Chuanqing Mao
- Department of Oral Surgery, The Union Hospital of Fujian Medical University , Fuzhou, Fujian, P.R. China
| | - Jin Wang
- Department of Oral Surgery, The Union Hospital of Fujian Medical University , Fuzhou, Fujian, P.R. China
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He T, Chen P, Jin L, Hu J, Li Y, Zhou L, Yang S, Mao X, Gui Y, Chen Y, Lai Y. miR‑660‑5p is associated with cell migration, invasion, proliferation and apoptosis in renal cell carcinoma. Mol Med Rep 2018; 17:2051-2060. [PMID: 29138826 DOI: 10.3892/mmr.2017.8052] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Accepted: 09/07/2017] [Indexed: 11/06/2022] Open
Abstract
Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system with poor prognosis. microRNAs (miRNAs) are a class of small, non‑coding RNA molecules that serve important roles in biological and pathological processes in several types of human tumors. miRNA (miR)‑660‑5p is dysregulated in many human cancers; however, its role in renal cell carcinoma is currently unclear. In the present study, reverse transcription‑quantitative polymerase chain reaction was performed to examine the expression levels of miR‑660‑5p in RCC tissues and paired normal adjacent tissues (NATs). To determine the function of miR‑660‑5p in RCC cells, wound‑healing and Matrigel assays were performed to determine the effects of miR‑660‑5p on cell migration and invasion, respectively. MTT and Cell Counting kit‑8 assays were performed to determine the effects of miR‑660‑5p on RCC cell proliferation. In addition, flow cytometric analysis was performed to validate the effects of miR‑660‑5p on apoptosis. The results indicated that miR‑660‑5p expression was downregulated in RCC tissues compared with NATs. Restoration of miR‑660‑5p expression using synthetic mimics may suppress cell migration, invasion and proliferation, and induce cell apoptosis, while using synthetic inhibitors may promote cell migration, invasion and proliferation, and suppress cell apoptosis. These results suggested that miR‑660‑5p may serve a tumor suppressive role in RCC tumorigenesis.
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Affiliation(s)
- Tao He
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Peijie Chen
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Lu Jin
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Jia Hu
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Yifan Li
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Liang Zhou
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Shangqi Yang
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Xiangming Mao
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Yaoting Gui
- The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China
| | - Yun Chen
- Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Yongqing Lai
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
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Pfreundschuh M. Age and Sex in Non-Hodgkin Lymphoma Therapy: It's Not All Created Equal, or Is It? Am Soc Clin Oncol Educ Book 2017; 37:505-511. [PMID: 28561693 DOI: 10.1200/edbk_175447] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Age is the most prominent factor for survival in all patients diagnosed with lymphoma, and male sex implies an increased and independent risk for a worse progression-free survival (PFS) and overall survival (OS) in most lymphomas, possibly with the exception of mantle cell lymphoma (MCL). The worse outcome for elderly patients is only partially explained by decreased tolerance to treatment regimens associated with the increasing number and severity of comorbidities. Little is known about specific differences in lymphoma biology with respect to age and sex, and this is changing only slowly despite the recent rise in interest about these issues. To better understand the differences and their underlying mechanisms, questions of age- and sex-specific outcomes, their correlation with pharmacokinetic data, and planned and received doses, must be addressed and reported in prospective clinical trials. Such studies must be accompanied by translational research that investigates biologic differences of lymphomas between old and young and male and female patients by addressing the microenvironment, cytogenetics including next-generation sequencing and systems biology of lymphomas, and correlation of these findings with treatment results. This knowledge will enable us to adjust lymphoma treatment to the necessities of more personalized medicine.
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Affiliation(s)
- Michael Pfreundschuh
- From the German High-Grade Non-Hodgkin Lymphoma Study Group, Internal Medicine I, Saarland University Medical School, Homburg, Germany
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