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Ma X, Zang X, Yang L, Zhou W, Li Y, Wei J, Guo J, Han J, Liang J, Jin T. Genetic polymorphisms in CYP2B6 may be associated with lung cancer risk in the Chinese Han population. Expert Rev Respir Med 2023; 17:1297-1305. [PMID: 38166557 DOI: 10.1080/17476348.2024.2302199] [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: 10/30/2023] [Accepted: 01/02/2024] [Indexed: 01/04/2024]
Abstract
BACKGROUND Our study aimed to elucidate the association between single nucleotide polymorphisms (SNPs) in CYP2B6 gene and susceptibility to lung cancer (LC). METHODS Five SNPs in CYP2B6 were genotyped in Chinese Han population (507 cases and 505 controls) utilizing Agena MassARRAY. The relationship between these SNPs and LC susceptibility was assessed using odds ratios, 95% confidence intervals, and χ2 tests. Additionally, multifactor dimensionality reduction was employed to analyze SNP-SNP interactions. Bioinformatics methods were applied to investigate the function of these SNPs. RESULTS We found that rs2099361 was associated with an increased susceptibility to LC in the codominant model (OR = 1.31, p = 0.045). Stratification analysis revealed the allele G at rs4803418 and the allele T at rs4803420 of CYP2B6 (BMI >24 kg/m2) were significantly linked to decreased susceptibility of LC. Conversely, the allele C at rs12979270 (BMI >24 kg/m2) showed increased susceptibility to LC. Moreover, a robust redundant relationship between rs12979270 and rs4803420 was identified in the study. According to the VannoPortal database, we found that rs4803420, rs12979270 and rs2099361 may modulate the binding affinity of LMNB1, SP1 and HDAC2, respectively. CONCLUSIONS Our results suggest that SNPs in the CYP2B6 gene play crucial roles in LC susceptibility.
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Affiliation(s)
- Xiaoya Ma
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi'an, Shaanxi, China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi, China
- Biomedicine Key Laboratory of Shaanxi Province, Northwest University, Xi'an, China
| | - Xufeng Zang
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi'an, Shaanxi, China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi, China
- Biomedicine Key Laboratory of Shaanxi Province, Northwest University, Xi'an, China
| | - Leteng Yang
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi'an, Shaanxi, China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi, China
- Biomedicine Key Laboratory of Shaanxi Province, Northwest University, Xi'an, China
| | - Wenqian Zhou
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi'an, Shaanxi, China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi, China
- Biomedicine Key Laboratory of Shaanxi Province, Northwest University, Xi'an, China
| | - Yujie Li
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi'an, Shaanxi, China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi, China
- Biomedicine Key Laboratory of Shaanxi Province, Northwest University, Xi'an, China
| | - Jie Wei
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi'an, Shaanxi, China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi, China
- Biomedicine Key Laboratory of Shaanxi Province, Northwest University, Xi'an, China
| | - Jinping Guo
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi'an, Shaanxi, China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi, China
- Biomedicine Key Laboratory of Shaanxi Province, Northwest University, Xi'an, China
| | - Junhui Han
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi'an, Shaanxi, China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi, China
- Biomedicine Key Laboratory of Shaanxi Province, Northwest University, Xi'an, China
| | - Jing Liang
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi'an, Shaanxi, China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi, China
- Biomedicine Key Laboratory of Shaanxi Province, Northwest University, Xi'an, China
| | - Tianbo Jin
- Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi'an, Shaanxi, China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, Shaanxi, China
- Biomedicine Key Laboratory of Shaanxi Province, Northwest University, Xi'an, China
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Wang Q, Wu H, Wu Q, Zhong S. Berberine targets KIF20A and CCNE2 to inhibit the progression of nonsmall cell lung cancer via the PI3K/AKT pathway. Drug Dev Res 2023; 84:907-921. [PMID: 37070571 DOI: 10.1002/ddr.22061] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 02/27/2023] [Accepted: 04/03/2023] [Indexed: 04/19/2023]
Abstract
BACKGROUND Nonsmall cell lung cancer (NSCLC) is the main type of lung cancer, accounting for approximately 85%. Berberine (BBR), a commonly used traditional Chinese medicine, has been reported to exhibit a potential antitumor effect in various cancers. In this research, we explored the function of BBR and its underlying mechanisms in the development of NSCLC. METHODS Cell Counting Kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), colony formation assays, flow cytometry, and transwell invasion assay were employed to determine cell growth, the apoptotic rate, cell invasion of NSCLC cells, respectively. Western blot was applied for detecting the protein expression of c-Myc, matrix metalloprotease 9 (MMP9), kinesin family member 20A (KIF20A), cyclin E2 (CCNE2), and phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway-related proteins. Glycolysis was evaluated by detecting glucose consumption, lactate production, and adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio with the matched kits. Real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to analyze the level of KIF20A and CCNE2. Tumor model was established to evaluate the function of BBR on tumor growth in NSCLC in vivo. In addition, immunohistochemistry assay was employed to detect the level of KIF20A, CCNE2, c-Myc, and MMP9 in mice tissues. RESULTS BBR exhibited suppressive effects on the progression of NSCLC, as evidenced by inhibiting cell growth, invasion, glycolysis, and facilitating cell apoptosis in H1299 and A549 cells. KIF20A and CCNE2 were upregulated in NSCLC tissues and cells. Moreover, BBR treatment significantly decreased the expression of KIF20A and CCNE2. KIF20A or CCNE2 downregulation could repress cell proliferation, invasion, glycolysis, and induce cell apoptosis in both H1299 and A549 cells. The inhibition effects of BBR treatment on cell proliferation, invasion, glycolysis, and promotion effect on cell apoptosis were rescued by KIF20A or CCNE2 overexpression in NSCLC cells. The inactivation of PI3K/AKT pathway caused by BBR treatment in H1299 and A549 cells was restored by KIF20A or CCNE2 upregulation. In vivo experiments also demonstrated that BBR treatment could repress tumor growth by regulating KIF20A and CCNE2 and inactivating the PI3K/AKT pathway. CONCLUSION BBR treatment showed the suppressive impact on the progression of NSCLC by targeting KIF20A and CCNE2, thereby inhibiting the activation of the PI3K/AKT pathway.
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Affiliation(s)
- Qi Wang
- Department of Thoracic Surgery, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, China
| | - Hua Wu
- Department of Thoracic Surgery, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, China
| | - Qingquan Wu
- Department of Thoracic Surgery, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, China
| | - Sheng Zhong
- Department of Thoracic Surgery, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, China
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Wu J, Zhang L, Liu H, Zhang J, Tang P. Exosomes promote hFOB1.19 proliferation and differentiation via LINC00520. J Orthop Surg Res 2023; 18:546. [PMID: 37516879 PMCID: PMC10387216 DOI: 10.1186/s13018-023-04021-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 07/15/2023] [Indexed: 07/31/2023] Open
Abstract
BACKGROUND Osteoporosis remains a significant clinical challenge worldwide. Recent studies have shown that exosomes stimulate bone regeneration. Thus, it is worthwhile to explore whether exosomes could be a useful therapeutic strategy for osteoporosis. The purpose of this study was to investigate the effects of exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) on osteoblast proliferation and differentiation. METHODS Exosomes were isolated from hucMSCs. Bioinformatics analysis was performed to identify the differentially expressed lncRNAs in myeloma-derived mesenchymal stem cells. Plasmids encoding LINC00520 or short hairpin RNA of LINC00520 were transfected into hucMSCs and then exosomes were isolated. After human osteoblasts hFOB1.19 were exposed to the obtained exosomes, cell survival, cell cycle, apoptosis and calcium deposits of hFOB1.19 cell were detected by MTT, 7-aminoactinomycin D, Annexin V-FITC/propidium iodide and Alizarin red staining, respectively. RESULTS In hFOB1.19 cells, 10 × 109/mL hucMSC-derived exosomes inhibited cell proliferation, arrested cell cycle, and promoted apoptosis, while hucMSCs or 1 × 109/mL exosomes promoted cell proliferation, accelerated cell cycle, and promoted calcium deposits and the expression of OCN, RUNX2, collagen I and ALP. In hFOB1.19 cells, exosomes from hucMSCs with LINC00520 knockdown reduced the survival and calcium deposits, arrested the cell cycle, and enhanced the apoptosis, while exosomes from hucMSCs overexpressing LINC00520 enhance the proliferation and calcium deposits and accelerated the cell cycle. CONCLUSIONS LINC00520 functions as a modulator of calcium deposits, and exosomes derived from hucMSCs overexpressing LINC00520 might be a novel therapeutic approach for osteoporosis.
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Affiliation(s)
- Jin Wu
- Medical School of Chinese PLA, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China
- Department of Orthopedics, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Chinese PLA General Hospital, Beijing, 100853, China
- Department of Orthopedics, The 909th Hospital, School of Medicine, Xiamen University, Zhangzhou, 363000, China
| | - Licheng Zhang
- Medical School of Chinese PLA, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
- Department of Orthopedics, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Chinese PLA General Hospital, Beijing, 100853, China.
| | - Hui Liu
- Department of Orthopedics, The 909th Hospital, School of Medicine, Xiamen University, Zhangzhou, 363000, China
| | - Jinhui Zhang
- Department of Orthopedics, The 909th Hospital, School of Medicine, Xiamen University, Zhangzhou, 363000, China
| | - Peifu Tang
- Medical School of Chinese PLA, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
- Department of Orthopedics, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Chinese PLA General Hospital, Beijing, 100853, China.
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Abstract
The specificity protein (Sp) transcription factors (TFs) Sp1, Sp2, Sp3 and Sp4 exhibit structural and functional similarities in cancer cells and extensive studies of Sp1 show that it is a negative prognostic factor for patients with multiple tumor types. In this review, the role of Sp1, Sp3 and Sp4 in the development of cancer and their regulation of pro-oncogenic factors and pathways is reviewed. In addition, interactions with non-coding RNAs and the development of agents that target Sp transcription factors are also discussed. Studies on normal cell transformation into cancer cell lines show that this transformation process is accompanied by increased levels of Sp1 in most cell models, and in the transformation of muscle cells into rhabdomyosarcoma, both Sp1 and Sp3, but not Sp4, are increased. The pro-oncogenic functions of Sp1, Sp3 and Sp4 in cancer cell lines were studied in knockdown studies where silencing of each individual Sp TF decreased cancer growth, invasion and induced apoptosis. Silencing of an individual Sp TF was not compensated for by the other two and it was concluded that Sp1, Sp3 and Sp4 are examples of non-oncogene addicted genes. This conclusion was strengthened by the results of Sp TF interactions with non-coding microRNAs and long non-coding RNAs where Sp1 contributed to pro-oncogenic functions of Sp/non-coding RNAs. There are now many examples of anticancer agents and pharmaceuticals that induce downregulation/degradation of Sp1, Sp3 and Sp4, yet clinical applications of drugs specifically targeting Sp TFs are not being used. The application of agents targeting Sp TFs in combination therapies should be considered for their potential to enhance treatment efficacy and decrease toxic side effects.
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Affiliation(s)
- Stephen Safe
- Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA
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Long Intergenic Non-Protein Coding RNA 173 in Human Cancers. Cancers (Basel) 2022; 14:cancers14235923. [PMID: 36497407 PMCID: PMC9737410 DOI: 10.3390/cancers14235923] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Revised: 11/23/2022] [Accepted: 11/25/2022] [Indexed: 12/05/2022] Open
Abstract
Long non-coding RNAs belong to non-coding RNAs (ncRNAs) with a length of more than 200 nucleotides and limited protein-coding ability. Growing research has clarified that dysregulated lncRNAs are correlated with the development of various complex diseases, including cancer. LINC00173 has drawn researchers' attention as one of the recently discovered lncRNAs. Aberrant expression of LINC00173 affects the initiation and progression of human cancers. In the present review, we summarize the recent considerable research on LINC00173 in 11 human cancers. Through the summary of the abnormal expression of LINC00173 and its potential molecular regulation mechanism in cancers, this article indicates that LINC00173 may serve as a potential diagnostic biomarker and a target for drug therapy, thus providing novel clues for future related research.
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Guo Y, Feng L. N6-methyladenosine-mediated upregulation of LINC00520 accelerates breast cancer progression via regulating miR-577/POSTN axis and downstream ILK/AKT/mTOR signaling pathway. Arch Biochem Biophys 2022; 729:109381. [PMID: 36027936 DOI: 10.1016/j.abb.2022.109381] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 08/03/2022] [Accepted: 08/18/2022] [Indexed: 11/19/2022]
Abstract
Various lncRNAs have been reported to be closely associated with cancer initiation and progression in breast cancer (BC), including LINC00520. However, the role and underlying mechanisms by which LINC00520 affects BC aggressiveness have not been fully delineated, and this study aimed to explore this issue. Through performing qRT-PCR analysis, we proved that LINC00520 was significantly upregulated in BC tissues and cells, compared with normal tissues and cells. Higher expression of LINC00520 was closely related to higher tumor grade, poor differentiation and shorter survival in BC patients. Next, the loss-of-function experiments evidenced that silencing LINC00520 suppressed BC cell proliferation, migration and epithelial-mesenchymal transition (EMT) in vitro, and inhibited tumorigenesis in vivo. Interestingly, we found that LINC00520 expression was positively regulated by METTL3-mediated N6-methyladenosine(m6A) modification in BC. Furthermore, we identified the tumor-suppressor miR-577 as the binding target of LINC00520 in BC. Mechanistically, LINC00520 elevated POSTN level via sponging miR-577, resulting in the activation of the downstream tumor-promoting ILK/Akt/mTOR pathway. Finally, the rescuing experiments evidenced that both POSTN knockdown and ILK/Akt/mTOR pathway inhibitor OSU-T315 abrogated the promoting effects of miR-577 ablation on the malignant phenotypes in BC. Collectively, this study firstly verified that LINC00520 acted as a ceRNA of miR-577 to advance BC aggressiveness in a m6A-dependent manner, providing novel biomarkers for BC diagnosis and therapy.
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Affiliation(s)
- Yang Guo
- Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
| | - Liang Feng
- Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
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STAT3-mediated upregulation of LINC00520 contributed to temozolomide chemoresistance in glioblastoma by interacting with RNA-binding protein LIN28B. Cancer Cell Int 2022; 22:248. [PMID: 35945579 PMCID: PMC9361558 DOI: 10.1186/s12935-022-02659-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 07/19/2022] [Indexed: 11/30/2022] Open
Abstract
A considerable number of glioblastoma (GBM) patients developed drug resistance to Temozolomide (TMZ) during chemotherapy, resulting in therapeutic failure and tumor recurrence. However, the exact mechanism of TMZ chemoresistance in GBM is still poorly clarified. As a novel identified lncRNA, LINC00520 was located on chromosome 14 and overexpressed in multiple human cancers. This study was designed and conducted to investigate the role and underlying mechanism of LINC00520 in GBM chemoresistance to TMZ. The qRT-PCR assay demonstrated that LINC00520 was significantly overexpressed in TMZ-sensitive and/or TMZ-resistant GBM cells (P < 0.001). The silencing of LINC00520 markedly reduced the cell viability, suppressed colony formation, induced cell apoptosis and G1/S phase arrest in TMZ-resistant cells (P < 0.001). In contrast, overexpression of LINC00520 conferred TMZ-resistant phenotype of GBM cells in vitro (P < 0.001). The orthotopic xenograft model was established and the results indicated that the volume of tumor xenografts in vivo was markedly inhibited by TMZ treatment after the silencing of LINC00520 (P < 0.001). Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay revealed a strong affinity of transcription factor STAT3 to the promoter regions of LINC00520, suggesting that STAT3 mediated the aberrant expression of LINC00520 in GBM. Further experiments demonstrated that LINC00520 could interact with RNA-binding protein LIN28B to inhibit autophagy and reduce DNA damage, thereby contributing to TMZ chemoresistance in GBM. These findings suggested that STAT3/LINC00520/LIN28B axis might be a promising target to improve TMZ chemoresistance of GBM.
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Zhao F, Li S, Liu J, Wang J, Yang B. Long non-coding RNA TRIM52-AS1 sponges microRNA-577 to facilitate diffuse large B cell lymphoma progression via increasing TRIM52 expression. Hum Cell 2022; 35:1234-1247. [PMID: 35676608 DOI: 10.1007/s13577-022-00725-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 05/13/2022] [Indexed: 11/04/2022]
Abstract
Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL) globally, featuring heterogeneous clinical phenotypes and altered molecular manifestations. The long non-coding ribose nucleic acids (lncRNAs) play crucial roles in the diagnosis, treatment, and prognosis of DLBCL, requiring the exploration of complex functions and mechanisms. In this study, the expression of lncRNA TRIM52-AS1 in DLBCL tissues from the Cancer Genome Atlas (TCGA) database was initially analyzed and correlated to the data from collected clinical samples. Then, the significance of TRIM52-AS1 on the diagnosis and prognosis of DLBCL patients was predicted with the receiver-operating characteristic (ROC) curve and Kaplan-Meier (KM) analysis. Further, cell counting kit (CCK)-8, EdU staining, and flow cytometry analyses were performed to assess the effect of TRIM52-AS1 on DLBCL cell proliferation, apoptosis, and cell cycle. Then, the mechanism of TRIM52-AS1 sponging miR-577 to increase TRIM52 expression was explored using a starBase prediction approach, dual-luciferase reporter, RNA immunoprecipitation assay (RIPA), quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and Western blot analyses. The experimental results confirmed the overexpression of TRIM52-AS1 in the DLBCL cell lines. Further, the high expression of TRIM52-AS1 predicted the poor Ann Arbor stage and were correlated with the presence of B symptoms, high international prognostic index, and poor disease prognosis. TRIM52-AS1 knockdown inhibited the DLBCL cell proliferation, and induced apoptosis and G0/G1 cycle arrest. Interestingly, the overexpression of TRIM52-AS1 increased the mRNA stability of TRIM52 through binding IGFBP3 protein and upregulated the TRIM52 protein expression by sponging miR-577. Together, the overexpressed TRIM52-AS1 could promote the DLBCL progression through IGFBP3/miR-218-5p/TRIM52 axis, highlighting the clinical significance of TRIM52-AS1 in the DLBCL diagnosis.
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Affiliation(s)
- Fang Zhao
- Department of Hematology, Cangzhou Central Hospital, 16 Middle Xinhua Road, Cangzhou, 061000, Hebei, China.
| | - Shucheng Li
- Department of Hematology, Cangzhou Central Hospital, 16 Middle Xinhua Road, Cangzhou, 061000, Hebei, China
| | - Jingjing Liu
- Department of Hematology, Cangzhou Central Hospital, 16 Middle Xinhua Road, Cangzhou, 061000, Hebei, China
| | - Juan Wang
- Department of Hematology, Cangzhou Central Hospital, 16 Middle Xinhua Road, Cangzhou, 061000, Hebei, China
| | - Bo Yang
- Department of Thoracic Surgery, Cangzhou Central Hospital, Cangzhou, Hebei, China
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Zhang Q, Shen J, Wu Y, Ruan W, Zhu F, Duan S. LINC00520: A Potential Diagnostic and Prognostic Biomarker in Cancer. Front Immunol 2022; 13:845418. [PMID: 35309319 PMCID: PMC8924041 DOI: 10.3389/fimmu.2022.845418] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 02/15/2022] [Indexed: 11/13/2022] Open
Abstract
Long non-coding RNA (lncRNA) is important in the study of cancer mechanisms. LINC00520 is located on human chromosome 14q22.3 and is a highly conserved long non-coding RNA. LINC00520 is widely expressed in various tissues. The expression of LINC00520 is regulated by transcription factors such as Sp1, TFAP4, and STAT3. The high expression of LINC00520 is significantly related to the risk of 11 cancers. LINC00520 can competitively bind 10 miRNAs to promote tumor cell proliferation, invasion, and migration. In addition, LINC00520 is involved in the regulation of P13K/AKT and JAK/STAT signaling pathways. The expression of LINC00520 is significantly related to the clinicopathological characteristics and prognosis of tumor patients and is also related to the sensitivity of HNSCC to radiotherapy. Here, this article summarizes the abnormal expression pattern of LINC00520 in cancer and its potential molecular regulation mechanism and points out that LINC00520 can be used as a potential biomarker for cancer diagnosis, prognosis, and treatment.
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Affiliation(s)
- Qiudan Zhang
- School of Medicine, Zhejiang University City College, Hangzhou, China.,Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, China
| | - Jinze Shen
- School of Medicine, Zhejiang University City College, Hangzhou, China
| | - Yuchen Wu
- Department of Clinical Medicine, The First School of Medicine, Wenzhou Medical University, Wenzhou, China
| | - Wenjing Ruan
- Department of Respiratory Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Feng Zhu
- School of Medicine, Zhejiang University City College, Hangzhou, China
| | - Shiwei Duan
- School of Medicine, Zhejiang University City College, Hangzhou, China.,Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, China
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Qiu Y, Wang HT, Zheng XF, Huang X, Meng JZ, Huang JP, Wen ZP, Yao J. Autophagy-related long non-coding RNA prognostic model predicts prognosis and survival of melanoma patients. World J Clin Cases 2022; 10:3334-3351. [PMID: 35611195 PMCID: PMC9048552 DOI: 10.12998/wjcc.v10.i11.3334] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/29/2021] [Accepted: 01/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Melanomas are malignant tumors that can occur in different body parts or tissues such as the skin, mucous membrane, uvea, and pia mater. Long non-coding RNAs (lncRNAs) are key factors in the occurrence and development of many malignant tumors, and are involved in the prognosis of some patients.
AIM To identify autophagy-related lncRNAs in melanoma that are crucial for the diagnosis, treatment, and prognosis of melanoma patients.
METHODS We retrieved transcriptome expression profiles and clinical information of 470 melanoma patients from The Cancer Genome Atlas (TCGA) database. Then, we identified autophagy-related genes in the Human Autophagy Database. Using R, coexpression analysis of lncRNAs and autophagy-related genes was conducted to obtain autophagy-related lncRNAs and their expression levels. We also performed univariate and multivariate Cox proportional risk analyses on the obtained datasets, to systematically evaluate the prognostic value of autophagy-related lncRNAs in melanoma. Fifteen autophagy-related lncRNAs were identified and an autophagy-related prognostic signature for melanoma was established. The Kaplan-Meier and univariate and multivariate Cox regression analyses were used to calculate risk scores. Based on the risk scores, melanoma patients were randomly divided into high- and low-risk groups. Receiver operating characteristic curve analysis, dependent on time, was performed to assess the accuracy of the prognostic model. At the same time, we also downloaded the melanoma data sets GSE65904, GSE19234, and GSE78220 from the GENE EXPRESSION OMNIBUS database for model verification. Finally, we performed Gene Set Enrichment Analysis functional annotation, which showed that the low and the high-risk groups had different enriched pathways.
RESULTS The co-expression network for autophagy-related genes was constructed using R, and 936 lncRNAs related to autophagy were identified. Then, 52 autophagy-related lncRNAs were significantly associated with TCGA melanoma patients’ survival by univariate Cox proportional risk analysis (P < 0.01). Further, the 52 autophagy-related lncRNAs mentioned above were analyzed by multivariate Cox analysis with R. Fifteen lncRNAs were selected: LINC01943, AC090948.3, USP30-AS1, AC068282.1, AC004687.1, AL133371.2, AC242842.1, PCED1B-AS1, HLA-DQB1-AS1, AC011374.2, LINC00324, AC018553.1, LINC00520, DBH-AS1, and ITGB2-AS1. The P values in all survival analyses using these 15 lncRNAs were < 0.05. These lncRNAs were used to build a risk model based on the risk score. Negative correlations were observed between risk scores and overall survival rate in melanoma patients over time. Additionally, the melanoma risk curve and scatter plot analyses showed that the death number increased along with the increase in the risk score. Overall, we identified and established a new prognostic risk model for melanoma using 15 autophagy-related lncRNAs. The risk model constructed with these lncRNAs can help and guide melanoma patient prognosis predictions and individualized treatments in the future.
CONCLUSION Overall, the risk model developed based on the 15 autophagy-related lncRNAs can have important prognostic value and may provide autophagy-related clinical targets for melanoma treatment.
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Affiliation(s)
- Yue Qiu
- Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
- Department of Bone and Joint Surgery, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Hong-Tao Wang
- Department of Orthopedics, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Xi-Fan Zheng
- Department of Bone and Joint Surgery, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Xing Huang
- Department of Bone and Joint Surgery, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Jin-Zhi Meng
- Department of Bone and Joint Surgery, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Jun-Pu Huang
- Department of Bone and Joint Surgery, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Zhen-Pei Wen
- Department of Bone and Joint Surgery, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Jun Yao
- Department of Orthopedics, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China
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Xu L, Huang X, Lou Y, Xie W, Zhao H. Regulation of apoptosis, autophagy and ferroptosis by non‑coding RNAs in metastatic non‑small cell lung cancer (Review). Exp Ther Med 2022; 23:352. [PMID: 35493430 PMCID: PMC9019694 DOI: 10.3892/etm.2022.11279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 03/10/2022] [Indexed: 11/06/2022] Open
Abstract
Non-small cell lung cancer (NSCLC), a common type of cancer worldwide, is normally associated with a poor prognosis. It is difficult to treat successfully as it often metastasizes into brain or bone. Methods to facilitate the induction of effective programmed cell death (PCD) in NSCLC cells to reverse drug resistance, or to inhibit the invasion and migration of NSCLC cells, are currently under investigation. The present study summarized the regulatory functions of PCD, including apoptosis, autophagy and ferroptosis, in the context of NSCLC metastasis. It further summarized how regulatory agents, including long non-coding RNAs, circular RNAs and microRNAs, regulate PCD during the metastasis of NSCLC and characterized new potential diagnostic biomarkers of NSCLC metastasis.
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Affiliation(s)
- Lei Xu
- Department of Orthopedics, Chengdu Seventh People's Hospital, Chengdu, Sichuan 610213, P.R. China
| | - Xin Huang
- Department of Orthopedics, Chengdu Seventh People's Hospital, Chengdu, Sichuan 610213, P.R. China
| | - Yan Lou
- Department of Orthopedic Oncology, Spine Tumor Center, Changzheng Hospital, Naval Military Medical University, Shanghai 200003, P.R. China
| | - Wei Xie
- Department of Orthopedics, Chengdu Seventh People's Hospital, Chengdu, Sichuan 610213, P.R. China
| | - Hangyu Zhao
- Department of Orthopedics, Chengdu Seventh People's Hospital, Chengdu, Sichuan 610213, P.R. China
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12
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Li Q, Wang W, Yang T, Li D, Huang Y, Bai G, Li Q. LINC00520 up-regulates SOX5 to promote cell proliferation and invasion by miR-4516 in human hepatocellular carcinoma. Biol Chem 2022; 403:665-678. [PMID: 35089659 DOI: 10.1515/hsz-2021-0316] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 01/05/2022] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common human cancers. Long non-coding RNA (lncRNA) has been demonstrated to play an important role in regulating tumor development. The current study aims to explore the specific role of LINC00520 during HCC progression. The present study identified that LINC00520 was upregulated in HCC tissues and indicated poor patient survival. Overexpression of LINC00520 promoted HCC cell proliferation, migration and invasion, while LINC00520 downregulation led to the opposite effects. Besides, LINC00520 knockdown was found to inhibit tumor growth in vivo. Furthermore, LINC00520 acted as a sponge of miR-4516 to regulate SRY-related high mobility group box 5 (SOX5). In addition, the inhibition of miR-4516 partly reversed the inhibitory effect of LINC00520 silencing on HCC cell proliferation, migration and invasion. In conclusion, the inhibition of LINC00520 suppressed HCC cell proliferation, migration and invasion through mediating miR-4516/SOX5 axis. Therefore, our study provides a basis for the development of treatment strategies for HCC.
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Affiliation(s)
- Qing Li
- Department of Internal Medicine, Third Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China
| | - Wei Wang
- Department of General Surgery, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China
| | - Tao Yang
- Department of General Surgery, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China
| | - Dongsheng Li
- Department of General Surgery, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China
| | - Yinpeng Huang
- Department of General Surgery, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China
| | - Guang Bai
- Department of General Surgery, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China
| | - Qiang Li
- Department of General Surgery, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China
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13
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Young MJ, Chen YC, Wang SA, Chang HP, Yang WB, Lee CC, Liu CY, Tseng YL, Wang YC, Sun HS, Chang WC, Hung JJ. Estradiol-mediated inhibition of Sp1 decreases miR-3194-5p expression to enhance CD44 expression during lung cancer progression. J Biomed Sci 2022; 29:3. [PMID: 35034634 PMCID: PMC8762881 DOI: 10.1186/s12929-022-00787-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 01/07/2022] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Sp1, an important transcription factor, is involved in the progression of various cancers. Our previous studies have indicated that Sp1 levels are increased in the early stage of lung cancer progression but decrease during the late stage, leading to poor prognosis. In addition, estrogen has been shown to be involved in lung cancer progression. According to previous studies, Sp1 can interact with the estrogen receptor (ER) to coregulate gene expression. The role of interaction between Sp1 and ER in lung cancer progression is still unknown and will be clarified in this study. METHODS The clinical relevance between Sp1 levels and survival rates in young women with lung cancer was studied by immunohistochemistry. We validated the sex dependence of lung cancer progression in EGFRL858R-induced lung cancer mice. Wound healing assays, chamber assays and sphere formation assays in A549 cells, Taxol-induced drug-resistant A549 (A549-T24) and estradiol (E2)-treated A549 (E2-A549) cells were performed to investigate the roles of Taxol and E2 in lung cancer progression. Luciferase reporter assays, immunoblot and q-PCR were performed to evaluate the interaction between Sp1, microRNAs and CD44. Tail vein-injected xenograft experiments were performed to study lung metastasis. Samples obtained from lung cancer patients were used to study the mRNA level of CD44 by q-PCR and the protein levels of Sp1 and CD44 by immunoblot and immunohistochemistry. RESULTS In this study, we found that Sp1 expression was decreased in premenopausal women with late-stage lung cancer, resulting in a poor prognosis. Tumor formation was more substantial in female EGFRL858R mice than in male mice and ovariectomized female mice, indicating that E2 might be involved in the poor prognosis of lung cancer. We herein report that Sp1 negatively regulates metastasis and cancer stemness in E2-A549 and A549-T24 cells. Furthermore, E2 increases the mRNA and protein levels of RING finger protein 4 (RNF4), which is the E3-ligase of Sp1, and thereby decreases Sp1 levels by promoting Sp1 degradation. Sp1 can be recruited to the promoter of miR-3194-5p, and positively regulate its expression. Furthermore, there was a strong inverse correlation between Sp1 and CD44 levels in clinical lung cancer specimens. Sp1 inhibited CD44 expression by increasing the expression of miR-3194-5p, miR-218-5p, miR-193-5p, miR-182-5p and miR-135-5p, ultimately resulting in lung cancer malignancy. CONCLUSION Premenopausal women with lung cancer and decreased Sp1 levels have a poor prognosis. E2 increases RNF4 expression to repress Sp1 levels in premenopausal women with lung cancer, thus decreasing the expression of several miRNAs that can target CD44 and ultimately leading to cancer malignancy.
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Affiliation(s)
- Ming-Jer Young
- Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwan
| | - Yung-Ching Chen
- Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwan
| | - Shao-An Wang
- School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Hui-Ping Chang
- Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwan
| | - Wen-Bin Yang
- TMU Research Center of Neuroscience, Taipei Medical University, 11031, Taipei, Taiwan
| | - Chia-Chi Lee
- Division of Thoracic Surgery, Department of Surgery, College of Medicine National, Cheng Kung University, Tainan, Taiwan
| | - Chia-Yu Liu
- Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwan
| | - Yau-Lin Tseng
- Division of Thoracic Surgery, Department of Surgery, College of Medicine National, Cheng Kung University, Tainan, Taiwan
| | - Yi-Ching Wang
- Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - H Sunny Sun
- Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wen-Chang Chang
- The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
| | - Jan-Jong Hung
- Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwan.
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
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Zhao D, Hou Y. Long non-coding RNA nuclear-enriched abundant transcript 1 (LncRNA NEAT1) upregulates Cyclin T2 (CCNT2) in laryngeal papilloma through sponging miR-577/miR-1224-5p and blocking cell apoptosis. Bioengineered 2022; 13:1828-1837. [PMID: 35012431 PMCID: PMC8805935 DOI: 10.1080/21655979.2021.2017653] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Long non-coding RNA nuclear-enriched abundant transcript 1 (Lnc-NEAT1) is a crucial mediator in cancer progression, which is associated with poor prognosis of patients with laryngeal papilloma (LP). Herein, we aimed to determine how Lnc-NEAT1 promotes LP development. q-PCR, MTT, EDU and Western blotting were performed to determine that Lnc-NEAT1 facilitates LP cell proliferation and hinders cell apoptosis. LncBase database, q-PCR, GEPIA online database, Dual luciferase reporter and RIP assays were utilized to confirm that Lnc-NEAT1 sponged miR-577/miR-1224-5p and negatively mediated CCNT2. Western blotting, MTT and EDU were used to confirm that Lnc-NEAT1 promoted LP cell proliferation and inhibited cell apoptosis through CCNT2. Lnc-NEAT1 was highly expressed in LP, and enhanced LP cell proliferation, and it was inhibited by Lnc-NEAT1 depleting. Concerning the underlying mechanism, it was found that Lnc-NEAT1 could functionally sponge microRNA-577 (miR-577) and microRNA-1224-5p (miR-1224-5p) and up-regulate Cyclin T2 (CCNT2) in LP cells. Notably, CCNT2 knockdown blocked Lnc-NEAT1-induced LP cell proliferation, and rescued cell apoptosis, which was specifically indicated by restoration of Bax, Cleaved caspase 3 and Cleaved caspase 9. Lnc-NEAT1 played a carcinogenic role in LP through mediating miR-577 or miR-1224-5p/CCNT2 axis, which may provide promising insights for the treatment of LP.
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Affiliation(s)
- Dong Zhao
- Department of Otolaryngology-Head and Neck Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yueting Hou
- Department of Otolaryngology-Head and Neck Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
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