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Gregorova J, Vlachova M, Vychytilova‐Faltejskova P, Dostalova A, Ruzickova T, Vecera M, Radova L, Pospichalova V, Sladecek S, Hyzdalova M, Kotaskova J, Jarosova M, Masek J, Benesova K, Jarkovsky J, Rihova L, Bezdekova R, Almasi M, Boichuk I, Stork M, Pour L, Sevcikova S. MicroRNA Profiling of Bone Marrow Plasma Extracellular Vesicles in Multiple Myeloma, Extramedullary Disease, and Plasma Cell Leukemia. Hematol Oncol 2025; 43:e70036. [PMID: 39804194 PMCID: PMC11727818 DOI: 10.1002/hon.70036] [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: 08/28/2024] [Revised: 12/09/2024] [Accepted: 01/03/2025] [Indexed: 01/16/2025]
Abstract
Multiple myeloma is a plasma cell malignancy characterized by an abnormal increase in monoclonal immunoglobulins. Despite significant advances in treatment, some patients progress to more aggressive forms of multiple myeloma, including extramedullary disease or plasma cell leukemia. Although the exact molecular mechanisms are not known, several studies have confirmed the involvement of small extracellular vesicle-enriched microRNAs in multiple myeloma progression. Therefore, we performed expression profiling of these molecules in bone marrow plasma of multiple myeloma, extramedullary disease, and plasma cell leukemia patients using small RNA sequencing to identify novel molecules involved in disease pathogenesis. In total, 42 microRNAs were significantly dysregulated among analyzed subgroups. Independent validation by RT-qPCR confirmed elevated levels of miR-140-3p, miR-584-5p, miR-191-5p, and miR-143-3p in multiple myeloma patients compared to extramedullary disease and plasma cell leukemia patients. Subsequent statistical analysis revealed significant correlations between patient clinical characteristics or flow cytometry parameters and microRNA expression. These results indicate that dysregulation of microRNAs could contribute to multiple myeloma progression.
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Affiliation(s)
- Jana Gregorova
- Babak Myeloma GroupDepartment of PathophysiologyFaculty of MedicineMasaryk UniversityBrnoCzech Republic
| | - Monika Vlachova
- Babak Myeloma GroupDepartment of PathophysiologyFaculty of MedicineMasaryk UniversityBrnoCzech Republic
| | | | - Adela Dostalova
- Babak Myeloma GroupDepartment of PathophysiologyFaculty of MedicineMasaryk UniversityBrnoCzech Republic
| | - Tereza Ruzickova
- Babak Myeloma GroupDepartment of PathophysiologyFaculty of MedicineMasaryk UniversityBrnoCzech Republic
| | - Marek Vecera
- Centre for Molecular MedicineCentral European Institute of TechnologyMasaryk UniversityBrnoCzech Republic
| | - Lenka Radova
- Centre for Molecular MedicineCentral European Institute of TechnologyMasaryk UniversityBrnoCzech Republic
| | - Vendula Pospichalova
- Department of Experimental BiologyFaculty of ScienceMasaryk UniversityBrnoCzech Republic
| | - Stanislava Sladecek
- Department of Experimental BiologyFaculty of ScienceMasaryk UniversityBrnoCzech Republic
| | - Martina Hyzdalova
- Department of Pharmacology and ToxicologyVeterinary Research InstituteBrnoCzech Republic
| | - Jana Kotaskova
- Department of Internal MedicineHematology and OncologyUniversity Hospital BrnoBrnoCzech Republic
| | - Marie Jarosova
- Department of Internal MedicineHematology and OncologyUniversity Hospital BrnoBrnoCzech Republic
| | - Josef Masek
- Department of Pharmacology and ToxicologyVeterinary Research InstituteBrnoCzech Republic
| | - Klara Benesova
- Faculty of MedicineInstitute of Biostatistics and AnalysesMasaryk UniversityBrnoCzech Republic
| | - Jiri Jarkovsky
- Faculty of MedicineInstitute of Biostatistics and AnalysesMasaryk UniversityBrnoCzech Republic
| | - Lucie Rihova
- Department of Clinical HematologyUniversity Hospital BrnoBrnoCzech Republic
| | - Renata Bezdekova
- Department of Clinical HematologyUniversity Hospital BrnoBrnoCzech Republic
| | - Martina Almasi
- Department of Clinical HematologyUniversity Hospital BrnoBrnoCzech Republic
| | - Ivanna Boichuk
- Department of Internal MedicineHematology and OncologyUniversity Hospital BrnoBrnoCzech Republic
| | - Martin Stork
- Department of Internal MedicineHematology and OncologyUniversity Hospital BrnoBrnoCzech Republic
| | - Ludek Pour
- Department of Internal MedicineHematology and OncologyUniversity Hospital BrnoBrnoCzech Republic
| | - Sabina Sevcikova
- Babak Myeloma GroupDepartment of PathophysiologyFaculty of MedicineMasaryk UniversityBrnoCzech Republic
- Department of Clinical HematologyUniversity Hospital BrnoBrnoCzech Republic
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Huang G, Liu Y, Li L, Li B, Jiang T, Cao Y, Yang X, Liu X, Qu H, Li S, Zheng X. Integration analysis of microRNAs as potential biomarkers in early-stage lung adenocarcinoma: the diagnostic and therapeutic significance of miR-183-3p. Front Oncol 2024; 14:1508715. [PMID: 39759146 PMCID: PMC11697600 DOI: 10.3389/fonc.2024.1508715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 12/03/2024] [Indexed: 01/07/2025] Open
Abstract
Introduction Lung adenocarcinoma (LUAD) poses a significant therapeutic challenge, primarily due to delayed diagnosis and the limited efficacy of existing treatments. Methods To understand the pathogenesis and identify diagnostic biomarkers for LUAD in the early stage, we investigated differential miRNA expression in 33 stage I LUAD patients between tumor and matched paracancerous tissues by Illumina Sequencing. Target genes of differentially expressed miRNAs were predicted using TargetScan and miRDB databases and further analyzed by GO and KEGG pathway enrichment analysis. The miRNAs expression results were verified using qRT-PCR. Additionally, we evaluated the clinical significance of miRNAs by the TCGA database. miR-183-3p was chosen for subsequent biological functional studies by cell proliferation assays, cell migration and cell invasion assays, cell apoptosis and cell cycle assays in LUAD cells. The clinical relevance target genes of miR-183-3p were predicted by TargetScan databases and bioinformatics assays. Gene-specific experimental validation was performed using qRT-PCR, western blotting and luciferase reporter assays. Results We identified 36 differentially expressed miRNAs between LUAD tissues and matched paracancerous tissues. Target genes for these miRNAs revealed associations with processes and pathways such as RNA biosynthesis, intracellular signaling, protein transport, and the Ras, MAPK, and PI3K-AKT pathways. The qRT-PCR results were in alignment with the sequencing data for 19 out of these 21 miRNAs which not yet implicated in LUAD, 13 were up-regulated, 6 were down-regulated. The clinical relevance assays showed that 5 up-regulated miRNAs have diagnostic value for LUAD. miR-183-3p showed significant advantages in the result of sequencing, qRT-PCR, and clinical relevance assay. Biological functional assays showed that miR-183-3p emerged as a key regulator, promoting LUAD cell proliferation, decreasing apoptosis, and augmenting migration and invasion capabilities. The clinical relevance assays and experimental validation showed SESN1 as a clinical significance target of miR-183-3p. Discussion Our study lays the foundation for investigating miRNAs with diagnostic significance in early-stage LUAD, pointing out that inhibition of miR-183-3p may serve as a novel therapeutic in LUAD.
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Affiliation(s)
- Guodong Huang
- Central Laboratory, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China
| | - Yuxia Liu
- Department of Respiration, Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Lisha Li
- Department of Respiration, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China
| | - Bing Li
- Central Laboratory, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China
| | - Ting Jiang
- Central Laboratory, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China
| | - Yufeng Cao
- Cancer Center, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China
| | - Xiaoping Yang
- Department of Respiration, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China
| | - Xinning Liu
- Central Laboratory, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China
| | - Honglin Qu
- Central Laboratory, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China
| | - Shitao Li
- Department of Respiration, Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Xin Zheng
- Central Laboratory, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, China
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Braile M, Luciano N, Carlomagno D, Salvatore G, Orlandella FM. Insight into the Role of the miR-584 Family in Human Cancers. Int J Mol Sci 2024; 25:7448. [PMID: 39000555 PMCID: PMC11242779 DOI: 10.3390/ijms25137448] [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: 05/31/2024] [Revised: 06/25/2024] [Accepted: 07/04/2024] [Indexed: 07/16/2024] Open
Abstract
Among the non-coding RNAs, the aberrant expression of microRNAs (miRNAs) is well described in the oncology field. It is clear that the altered expression of miRNAs is crucial for a variety of processes such as proliferation, apoptosis, motility, angiogenesis and metastasis insurgence. Considering these aspects, RNA-based therapies and the use of miRNAs as non-invasive biomarkers for early diagnosis are underlined as promising opportunities against cancer death. In the era of precision medicine, significant progress in next-generation sequencing (NGS) techniques has broadened knowledge regarding the miRNAs expression profile in cancer tissues and in the blood of cancer patients. In this scenario, pre-clinical and clinical studies suggested that the members of the miR-584 family, i.e., miR-584-5p and -3p, are prominent players in cancer development and progression. Under some conditions, these miRNAs are under-expressed in cancer tissues acting as tumor suppressors, while in other conditions, they are overexpressed, acting as oncogenes increasing the aggressive behavior of cancer cells. The aim of this review is to provide a comprehensive and up-to-date overview on the expression, upstream genes, molecular targets and signaling pathways influenced by the miR-584 family (i.e., miR-584-3p and -5p) in various human solid and hematological cancers. To achieve this goal, 64 articles on this topic are discussed. Among these articles, 55 are focused on miR-584-5p, and it is outlined how this miRNA could be used in future applications as a potential new therapeutic strategy and diagnostic tool.
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Affiliation(s)
| | - Neila Luciano
- Dipartimento di Scienze Biomediche Avanzate, Università degli Studi di Napoli “Federico II”, 80131 Naples, Italy;
| | - Davide Carlomagno
- Dipartimento di Farmacia, Università degli Studi di Napoli “Federico II”, 80131 Naples, Italy;
| | - Giuliana Salvatore
- CEINGE-Biotecnologie Avanzate Franco Salvatore, 80145 Naples, Italy;
- Dipartimento delle Scienze Mediche, Motorie e del Benessere, Università degli Studi di Napoli “Parthenope”, 80133 Naples, Italy
| | - Francesca Maria Orlandella
- CEINGE-Biotecnologie Avanzate Franco Salvatore, 80145 Naples, Italy;
- Dipartimento delle Scienze Mediche, Motorie e del Benessere, Università degli Studi di Napoli “Parthenope”, 80133 Naples, Italy
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Lu JJ, Shi XJ, Fu Q, Li YC, Zhu L, Lu N. MicroRNA-584-5p/RUNX family transcription factor 2 axis mediates hypoxia-induced osteogenic differentiation of periosteal stem cells. World J Stem Cells 2023; 15:979-988. [PMID: 37970237 PMCID: PMC10631372 DOI: 10.4252/wjsc.v15.i10.979] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 09/23/2023] [Accepted: 10/17/2023] [Indexed: 10/26/2023] Open
Abstract
BACKGROUND The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells (PSCs) into osteoblasts or chondrocytes; however, the underlying mechanisms remain unclear. AIM To determine the effect of hypoxia on PSCs, and the expression of microRNA-584-5p (miR-584-5p) and RUNX family transcription factor 2 (RUNX2) in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxia-induced osteogenic differentiation of PSCs. METHODS In this study, we isolated primary mouse PSCs and stimulated them with hypoxia, and the characteristics and functional genes related to PSC osteogenic differentiation were assessed. Constructs expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic differentiation. RESULTS Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules, intracellular calcium ion levels, and alkaline phosphatase (ALP) activity in PSCs. Osteogenic differentiation-related factors such as RUNX2, bone morphogenetic protein 2, hypoxia-inducible factor 1-alpha, and ALP were upregulated; in contrast, miR-584-5p was downregulated in these cells. Furthermore, upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic differentiation. RUNX2 was the target gene of miR-584-5p, antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic differentiation. CONCLUSION Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.
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Affiliation(s)
- Jia-Jia Lu
- Department of Orthopedic Trauma Surgery, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200001, China
- Department of Orthopedic Trauma Surgery, Shanghai Changzheng Hospital, Shanghai 200001, China
| | - Xiao-Jian Shi
- Department of Orthopedic Trauma, Haimen People's Hospital of Jiangsu Province, Nantong 226100, Jiangsu Province, China
| | - Qiang Fu
- Department of Orthopedic Trauma Surgery, Shanghai Changzheng Hospital, Shanghai 200001, China
| | - Yong-Chuan Li
- Department of Orthopedic Trauma Surgery, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200001, China
| | - Lei Zhu
- Department of Orthopedic Trauma Surgery, Shanghai Changzheng Hospital, Shanghai 200001, China
| | - Nan Lu
- Department of Orthopedic Trauma Surgery, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200001, China.
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Chen X, Li G, Zhong G, Chen J, Feng L, Zhang T, Tang Z. Long Non-Coding RNA DUXAP8 Acts as an Oncogene in Sinonasal Squamous Cell Carcinoma Through miR-584-5p/FNDC3B Pathway. Am J Rhinol Allergy 2022. [DOI: 10.110.1177/19458924221104919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Sinonasal squamous cell carcinoma (SNSCC) is one of the least frequent carcinomas in the head and neck and accounts for 60% to 75% of sinonasal malignancies. The role of long non-coding RNAs (lncRNAs) in cancer development has drawn great attention over the years. The current study intended to assess the role and specific mechanism of lncRNA double homeobox A pseudogene 8 (DUXAP8) in SNSCC. Quantitative real-time PCR (qRT-PCR) analysis was implemented to assess the expression level of DUXAP8, microRNA-584-5p (miR-584-5p), and fibronectin type III domain containing 3B (FNDC3B). Proliferation assays included colony formation assay, Cell Counting Kit-8 (CCK-8) assay, and 5-ethynyl-2′-deoxyuridine (EdU) assay. Transwell assays were implemented to monitor cell migration and invasion. Cell apoptosis was evaluated via terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) and JC-1 experiments. Mechanism experiments included RNA pull-down assay, RNA binding protein immunoprecipitation (RIP) assay, and luciferase reporter assay. DUXAP8 is overexpressed in SNSCC cells. Functionally, DUXAP8 silencing suppresses the malignant progression of SNSCC. Furthermore, DUXAP8 up-regulates the expression of FNDC3B via sponging miR-584-5p. Rescue experiments demonstrated that DUXAP8 mediates the progression of SNSCC via up-regulating FNDC3B expression. In conclusion, DUXAP8 acts as an oncogene in SNSCC, which may be a new molecular marker for SNSCC.
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Affiliation(s)
- Xuan Chen
- Department of Otolaryngology, Head and Neck Surgery, Shunde Hospital of Southern Medical University, Foshan, Guangdong Province, China
| | - Guidi Li
- Department of Otolaryngology, Head and Neck Surgery, Shunde Hospital of Southern Medical University, Foshan, Guangdong Province, China
| | - Guanzhong Zhong
- Department of Otolaryngology, Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University, Foshan, Guangdong Province, China
| | - Junyong Chen
- Department of Otolaryngology, Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University, Foshan, Guangdong Province, China
| | - Lijun Feng
- Department of Otolaryngology, Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University, Foshan, Guangdong Province, China
| | - Tao Zhang
- Department of Otolaryngology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China
| | - Zhi Tang
- Department of Otolaryngology, Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University, Foshan, Guangdong Province, China
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Li T, Liu H, Dong C, Lyu J. Application of miRNA Biomarkers in Predicting Overall Survival Outcomes for Lung Adenocarcinoma. BIOMED RESEARCH INTERNATIONAL 2022; 2022:5249576. [PMID: 36147635 PMCID: PMC9485713 DOI: 10.1155/2022/5249576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 08/25/2022] [Accepted: 09/01/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND With the development of research, the importance of microRNAs (miRNAs) in the occurrence, metastasis, and prognosis of lung adenocarcinoma (LUAD) has attracted extensive attention. This study is aimed at predicting overall survival (OS) results through bioinformatics to identify novel miRNA biomarkers and hub genes. MATERIALS AND METHODS The data of LUAD-related miRNA and mRNA samples was downloaded from The Cancer Genome Atlas (TCGA) database. Upon screening and pretreatment of initial data, TCGA data were analyzed using R platform and a series of analytical tools to identify biomarkers with high specificity and sensitivity. RESULTS 7 miRNAs and 13 hub genes that had strong relation to the overall surviving status were identified in patients with LUAD. The expression of seven miRNAs (hsa-miR-19a-3p, hsa-miR-126-5p, hsa-miR-556-3p, hsa-miR-671-5p, hsa-miR-937-3p, hsa-miR-4664-3p, and hsa-miR-4746-5p) could apparently improve the OS rate of patient with LUAD. The 13 hub genes, namely, CCT6A, CDK5R1, CEP55, DNAJB4, EGLN3, HDGF, HOXC8, LIMD1, MKI67, PCP4L1, PPIL1, SCAI, and STK32A, showed a correlation with the OS status. CONCLUSION 7 miRNAs were identified as novel biomarkers for the prognosis of patients with LUAD. This study offered a deeper comprehension of LUAD treatment and prognosis from the molecular level and helped enhance the understanding of the pathogenesis and potential molecular events of LUAD.
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Affiliation(s)
- Tingting Li
- Department of Pharmacy, Xi'an Chest Hospital, Xi'an, Shaanxi, China
| | - Huanqing Liu
- Northwestern Polytechnical University, Xi'an, Shaanxi, China
| | - Chunsheng Dong
- School of Computer Science, Shaanxi Normal University, Xi'an, Shaanxi, China
| | - Jun Lyu
- Northwestern Polytechnical University, Xi'an, Shaanxi, China
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
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Bai C, Yang W, Ouyang R, Li Z, Zhang L. Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma. Open Life Sci 2022; 17:726-734. [PMID: 35891968 PMCID: PMC9281586 DOI: 10.1515/biol-2022-0080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 04/18/2022] [Accepted: 04/26/2022] [Indexed: 11/18/2022] Open
Abstract
We detected the expressions of hsa_circRNA_000121 and hsa_circRNA_ 004183 in papillary thyroid microcarcinoma (PTMC) and explored their relationship with the invasiveness of PTMC. PTMC patients with (n = 30; metastasis group) and without lymph node metastasis (n = 30; nonmetastasis group) were included. The levels of hsa_circRNA_000121, hsa_circRNA_004183, hsa-miR-4763, hsa-miR-6775, sarcoma gene (SRC), and MMP-14 were detected with real-time polymerase chain reaction. Receiver-operating characteristic (ROC) analyzed the diagnostic value of hsa_circRNA_000121 and hsa_circRNA_004183. Binary logistic regression analysis evaluated the relationship of gene expression with PTMC invasiveness. In PTMC tissue samples, compared with the metastasis group, the expression of hsa_circRNA_000121, hsa_circRNA_004183, SRC, and MMP-14 in the nonmetastasis group decreased, while the expression of hsa-miR-4763 and hsa-miR-6775 increased. In peripheral blood, compared with the metastasis group, the expression of hsa_circ_000121 and hsa_circRNA_004183 in the nonmetastasis group decreased. Both hsa_circRNA_000121 and hsa_circRNA_004183 had good sensitivity and specificity for diagnosing PTMC lymph node metastasis, with a cut-off value of 0.796 and 0.938, respectively. However, the gene expressions were not significantly associated with PTMC lymph node metastasis. Hsa_circRNA_000121 may upregulate SRC expression through hsa-miR-4763, while hsa_circRNA 000121 may upregulate MMP-14 expression through hsa-miR-6775, thereby promoting the aggressiveness of PTMC and ultimately leading to cervical lymph node metastasis. hsa_circRNA_000121 and hsa_circRNA_004183 may become potential biomarkers of PTMC aggressiveness.
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Affiliation(s)
- Chao Bai
- Department of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China
| | - Wenwen Yang
- The Second Department of General Internal Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China
| | - Ru Ouyang
- Department of Endocrinology, Sanya Central Hospital, No. 1154, Jiefang 4th Road, Tianya District, Sanya 572000, China
| | - Zongbao Li
- Department of Endocrinology, Sanya Central Hospital, No. 1154, Jiefang 4th Road, Tianya District, Sanya 572000, China
| | - Li Zhang
- Department of Endocrinology, Sanya Central Hospital, No. 1154, Jiefang 4th Road, Tianya District, Sanya 572000, China
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Chen X, Li G, Zhong G, Chen J, Feng L, Zhang T, Tang Z. Long Non-Coding RNA DUXAP8 Acts as an Oncogene in Sinonasal Squamous Cell Carcinoma Through miR-584-5p/FNDC3B Pathway. Am J Rhinol Allergy 2022; 36:708-718. [PMID: 35695194 DOI: 10.1177/19458924221104919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Sinonasal squamous cell carcinoma (SNSCC) is one of the least frequent carcinomas in the head and neck and accounts for 60% to 75% of sinonasal malignancies. The role of long non-coding RNAs (lncRNAs) in cancer development has drawn great attention over the years. The current study intended to assess the role and specific mechanism of lncRNA double homeobox A pseudogene 8 (DUXAP8) in SNSCC. Quantitative real-time PCR (qRT-PCR) analysis was implemented to assess the expression level of DUXAP8, microRNA-584-5p (miR-584-5p), and fibronectin type III domain containing 3B (FNDC3B). Proliferation assays included colony formation assay, Cell Counting Kit-8 (CCK-8) assay, and 5-ethynyl-2'-deoxyuridine (EdU) assay. Transwell assays were implemented to monitor cell migration and invasion. Cell apoptosis was evaluated via terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) and JC-1 experiments. Mechanism experiments included RNA pull-down assay, RNA binding protein immunoprecipitation (RIP) assay, and luciferase reporter assay. DUXAP8 is overexpressed in SNSCC cells. Functionally, DUXAP8 silencing suppresses the malignant progression of SNSCC. Furthermore, DUXAP8 up-regulates the expression of FNDC3B via sponging miR-584-5p. Rescue experiments demonstrated that DUXAP8 mediates the progression of SNSCC via up-regulating FNDC3B expression. In conclusion, DUXAP8 acts as an oncogene in SNSCC, which may be a new molecular marker for SNSCC.
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Affiliation(s)
- Xuan Chen
- Department of Otolaryngology, Head and Neck Surgery, 477688Shunde Hospital of Southern Medical University, Foshan, Guangdong Province, China
| | - Guidi Li
- Department of Otolaryngology, Head and Neck Surgery, 477688Shunde Hospital of Southern Medical University, Foshan, Guangdong Province, China
| | - Guanzhong Zhong
- Department of Otolaryngology, Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University, Foshan, Guangdong Province, China
| | - Junyong Chen
- Department of Otolaryngology, Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University, Foshan, Guangdong Province, China
| | - Lijun Feng
- Department of Otolaryngology, Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University, Foshan, Guangdong Province, China
| | - Tao Zhang
- Department of Otolaryngology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China
| | - Zhi Tang
- Department of Otolaryngology, Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University, Foshan, Guangdong Province, China
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Downregulated long intergenic non-coding RNA 00,174 represses malignant biological behaviors of lung cancer cells by regulating microRNA-584-3p/ribosomal protein S24 axis. Funct Integr Genomics 2022; 22:643-653. [PMID: 35451652 DOI: 10.1007/s10142-022-00855-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 03/11/2022] [Accepted: 03/22/2022] [Indexed: 11/04/2022]
Abstract
The detailed regulatory mechanism of LINC00174 in lung cancer (LC) development remains largely unknown. This research was designed to probe into the impacts of LINC00174 in LC cells through modulating the microRNA (miR)-584-3p/ribosomal protein S24 (RPS24) axis. LINC00174, miR-584-3p, and RPS24 expression levels in LC cells and tissues were examined. The constructs altering LINC00174, miR-584-3p, or RPS24 expression were transfected into LC cells to examine the malignant phenotypes of LC cells. The relations among LINC00174, miR-584-3p, and RPS24 were validated. LINC00174 and RPS24 were high-expressed while miR-584-3p was low-expressed in LC. Downregulated LINC00174 or RPS24 or upregulated miR-584-3p inhibited the malignant biological behaviors of LC cells. The silenced miR-584-3p could reverse the repressive effects of reduced LINC00174 on the development of LC cells; while RPS24 overexpression inverted the repressive effects of miR-584-3p elevation on LC cells. Mechanically, LINC00174 bound to miR-584-3p that targeted RPS24. Repressed LINC00174 can relieve the malignant phenotypes of LC cells via modulating the miR-584-3p/RPS24 axis.
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Xiao H, Li Y, Zhang Y, Wang P. Long noncoding RNA LINC01296 regulates the cell proliferation, migration and invasion in neuroblastoma. Metab Brain Dis 2022; 37:1247-1258. [PMID: 35305236 DOI: 10.1007/s11011-022-00935-4] [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: 09/28/2021] [Accepted: 02/10/2022] [Indexed: 11/30/2022]
Abstract
Neuroblastoma (NB) is a childhood cancer that often occurs in the sympathetic nervous system. Previous reports showed that long non-coding RNAs (lncRNAs) could affect the progress of NB, but the mechanism is still indistinct. In this study, we unfolded the roles of LINC01296 in NB tissues and cells. The level of LINC01296, microRNA-584-5p (miR-584-5p), miR-34a-5p and mRNA of tripartite motif-containing 59 (TRIM59) were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) in NB tissues. The capacities of NB cells were validated by MTT assay, Edu assay, transwell assay and flow cytometry analysis. The interplay between miR-584-5p/miR-34a-5p and LINC01296 or TRIM59 were detected by dual-luciferase reporter assay. Finally, the in vivo experiment was implemented to verify the effect of LINC01296 in vivo. The level of LINC01296 and TRIM59 were increased, whereas miR-584-5p and miR-34a-5p levels were reduced in NB tissues in contrast to that in normal tissues. For functional analysis, LINC01296 deficiency inhibited the cell vitality, cell proliferation, migration and invasion in NB cells, whereas promoted cell apoptosis. Moreover, miR-584-5p and miR-34a-5p were validated to act as a tumor repressive effect in NB cells by restraining TRIM59. The results also showed that LINC01296 could regulate the development of NB. In mechanism, LINC01296 acted as a miR-584-5p and miR-34a-5p sponge to modulate TRIM59 expression. In addition, LINC01296 knockdown also attenuated tumor growth in vivo. LINC01296 promotes the progression of NB by increasing TRIM59 expression via regulating miR-584-5p and miR-34a-5p, which also offered an underlying targeted therapy for NB treatment.
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Affiliation(s)
- Huiling Xiao
- Department of Pediatrics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441000, China
| | - Yanhong Li
- Department of Pediatrics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441000, China
| | - Ying Zhang
- Department of Pediatrics, Xiangyang NO.1 People's Hospital Affiliated Hospital of Hubei University of Medicine, No.15, Jiefang Road, Fancheng District, Xiangyang, 441000, China.
| | - Peng Wang
- Department of Neurosurgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No.2, Chunyuandong Road, Fancheng District, Xiangyang, 441000, China.
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11
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Comprehensive Analysis of the Immune and Prognostic Implication of MMP14 in Lung Cancer. DISEASE MARKERS 2021; 2021:5917506. [PMID: 34868395 PMCID: PMC8635876 DOI: 10.1155/2021/5917506] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 10/27/2021] [Accepted: 11/01/2021] [Indexed: 12/22/2022]
Abstract
More and more studies have indicated an association between immune infiltration in lung cancer and clinical outcomes. Matrix metalloproteinase 14 (MMP14) has been reported to be dysregulated in many types of tumors and involved in the development and progression of tumors. However, its contribution to cancer immunity was rarely reported. In the study, we found that MMP14 expression was distinctly upregulated in lung cancer specimens compared with nontumor lung specimens. High MMP14 expression predicted a poor prognosis of lung squamous cell carcinoma (LUSC) patients. Increased MMP14 expressions were observed to be positively related to high immune infiltration levels in most of the immune cells. A pathway enrichment analysis of 32 MMP14-associated immunomodulators indicated the involvement of T cell receptor signaling pathway and Toll-like receptor signaling pathway. Based on MMP14-associated immunomodulators, we applied multivariate assays to construct multiple-gene risk prediction signatures. We observed that risk scores were independently associated with overall survival. These data highlighted that MMP14 was involved in tumor immunity, indicating that MMP14 could serve as a novel prognostic biomarker and therapeutic target for lung cancer. Our data suggest that the four genes identified in this study may serve as valuable biomarkers of lung cancer patient outcomes.
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12
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Tumor Suppressor miR-584-5p Inhibits Migration and Invasion in Smoking Related Non-Small Cell Lung Cancer Cells by Targeting YKT6. Cancers (Basel) 2021; 13:cancers13051159. [PMID: 33800298 PMCID: PMC7962648 DOI: 10.3390/cancers13051159] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 02/26/2021] [Accepted: 03/04/2021] [Indexed: 12/25/2022] Open
Abstract
Simple Summary Cigarette smoke is a major carcinogen that causes lung cancer and induces DNA methylation. DNA methylation regulates the expression of microRNA (miRNAs), which are important regulators of cancer biology. However, the association between smoking and miRNAs has not been fully elucidated in smoking-related lung carcinogenesis. In this study, we found that miR-584-5p expression was downregulated with cancer progression using a lung carcinogenesis model cell line. Moreover, we demonstrated that miR-584-5p is downregulated by the methylation of its promoter region and that it suppresses migration and invasion by targeting YKT6 in smoking-related non-small cell lung cancer (NSCLC) cells. Our results provide a better understanding of the underlying changes in miRNA expression in smoking-related lung carcinogenesis and suggest that miR-584-5p is a potential molecular biomarker for smoking-related NSCLC. Abstract Cigarette smoke (CS) affects the expression of microRNAs (miRNAs), which are important regulators of gene expression by inducing DNA methylation. However, the effects of smoking on miRNA expression have not been fully elucidated in smoking-related lung carcinogenesis. Therefore, in this study, to investigate the change of miRNA expression pattern and to identify tumor suppressor miRNAs by smoking in lung carcinogenesis, we used lung carcinogenesis model cell lines that, derived from a murine xenograft model with human bronchial epithelial cells (BEAS-2B), exposed CS or not. The microarray analysis revealed that miR-584-5p expression was downregulated with cancer progression in lung carcinogenesis model cell lines. We confirmed by pyrosequencing that the methylation level of the miR-584-5p promoter increased with cancer progression. In vitro and in vivo experiments showed that miR-584-5p suppressed migration and invasion in non-small cell lung cancer (NSCLC) cells by targeting YKT6. Furthermore, we showed that high level of YKT6 was associated with a poor survival rate in NSCLC patients with a history of smoking. These results suggest that miR-584-5p acts as a tumor suppressor and is a potential molecular biomarker for smoking-related NSCLC.
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13
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Ahn YH, Ko YH. Diagnostic and Therapeutic Implications of microRNAs in Non-Small Cell Lung Cancer. Int J Mol Sci 2020; 21:E8782. [PMID: 33233641 PMCID: PMC7699705 DOI: 10.3390/ijms21228782] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 11/11/2020] [Accepted: 11/12/2020] [Indexed: 02/07/2023] Open
Abstract
microRNAs (miRNAs), endogenous suppressors of target mRNAs, are deeply involved in every step of non-small cell lung cancer (NSCLC) development, from tumor initiation to progression and metastasis. They play roles in cell proliferation, apoptosis, angiogenesis, epithelial-to-mesenchymal transition, migration, invasion, and metastatic colonization, as well as immunosuppression. Due to their versatility, numerous attempts have been made to use miRNAs for clinical applications. miRNAs can be used as cancer subtype classifiers, diagnostic markers, drug-response predictors, prognostic markers, and therapeutic targets in NSCLC. Many challenges remain ahead of their actual clinical application; however, when achieved, the use of miRNAs in the clinic is expected to enable great progress in the diagnosis and treatment of patients with NSCLC.
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MESH Headings
- Antineoplastic Agents/therapeutic use
- Biomarkers, Pharmacological/analysis
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/immunology
- Carcinoma, Non-Small-Cell Lung/diagnosis
- Carcinoma, Non-Small-Cell Lung/drug therapy
- Carcinoma, Non-Small-Cell Lung/genetics
- Carcinoma, Non-Small-Cell Lung/immunology
- Cell Line, Tumor
- Cell Movement/drug effects
- Cell Proliferation/drug effects
- Epithelial-Mesenchymal Transition/drug effects
- Epithelial-Mesenchymal Transition/genetics
- Epithelial-Mesenchymal Transition/immunology
- Gene Expression Regulation, Neoplastic
- Humans
- Lung Neoplasms/diagnosis
- Lung Neoplasms/drug therapy
- Lung Neoplasms/genetics
- Lung Neoplasms/immunology
- Lymphatic Metastasis
- MicroRNAs/agonists
- MicroRNAs/antagonists & inhibitors
- MicroRNAs/genetics
- MicroRNAs/immunology
- Neovascularization, Pathologic/diagnosis
- Neovascularization, Pathologic/drug therapy
- Neovascularization, Pathologic/genetics
- Neovascularization, Pathologic/immunology
- Prognosis
- RNA, Messenger/genetics
- RNA, Messenger/immunology
- Signal Transduction
- Tumor Escape/drug effects
- Tumor Escape/genetics
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Affiliation(s)
- Young-Ho Ahn
- Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul 07804, Korea
- Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea
| | - Yoon Ho Ko
- Division of Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
- Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
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14
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Ma D, Qin Y, Huang C, Chen Y, Han Z, Zhou X, Liu H. Circular RNA ABCB10 promotes non-small cell lung cancer progression by increasing E2F5 expression through sponging miR-584-5p. Cell Cycle 2020; 19:1611-1620. [PMID: 32420810 PMCID: PMC7469616 DOI: 10.1080/15384101.2020.1761617] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Revised: 03/03/2020] [Accepted: 03/06/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND/AIMS CircABCB10 function as an endogenous miRNA sponge plays an important role in various tumors. This experimental design was based on circABCB10 to explore the pathogenesis of non-small cell lung cancer (NSCLC). Methods: CircRNA microarray was used to examine circRNA expression profiles in lung cancer from 3 NSCLC patients and paired healthy lung tissues. The expression of circABCB10 and miR-584-5p was detected by q-PCR. CCK-8, colony formation, and transwell assays to study the circABCB10 effects on tumor cell growth and cell migration invasiveness. To validate downstream target genes of circABCB10 and miR-584-5p detected by luciferase reporter assays. RT-qPCR and Western blotting were used to study E2F5 expression. The tumor growth was detected by nude mice in vivo. Results: We analyzed the human circRNA expression profile in NSCLC tissues. CircABCB10 was identified as a circRNA that increased in NSCLC tissues. CircABCB10 was noticeably raised in NSCLC, and high circABCB10 expression was related to low survival in NSCLC patients. Silencing of circABCB10 suppressed non-small cell lung cancer cell migration, cell proliferation, and invasion.CircABCB10 can act as a sponge of miR-584-5p to up-regulate E2F5 expression level. E2F5 knockdown or overexpress of miR-584-5p gene reversed the circABCB10 who has carcinogenic effects. There was a negative correlation expression between the circABCB10 and miR-584-5p gene, and There was a positive relationship between the expression of circABCB10 and E2F5 in NSCLC tumors. Conclusion: CircABCB10 promoted the progression of NSCLC by modulating the miR-584-5p/E2F5 axis. ABBREVIATION NSCLC: non-small cell lung cancer; circ RNA: circular RNA; miRNA: micro RNA.
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Affiliation(s)
- Dongjie Ma
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing City, PR. China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing City, PR. China
| | - Yingzhi Qin
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing City, PR. China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing City, PR. China
| | - Cheng Huang
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing City, PR. China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing City, PR. China
| | - Yeye Chen
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing City, PR. China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing City, PR. China
| | - Zhijun Han
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing City, PR. China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing City, PR. China
| | - Xiaoyun Zhou
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing City, PR. China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing City, PR. China
| | - Hongsheng Liu
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing City, PR. China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing City, PR. China
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