摘要
背景:非编码小RNA参与生物体的发育,其异常调控可引起包括肝细胞癌(HCC)在内的多种疾病,但其确切机制尚不清楚。目的:探讨miR-142-3p对肝细胞癌HMGB 1表达的影响。方法:采用RT-PCR方法检测肝癌组织和培养细胞中miR-142-3p的表达水平.采用Transwell迁移和侵袭试验检测HepG 2细胞的侵袭转移能力,Western印迹法检测其蛋白表达。结果:本研究报道miR-142-3p促进肝癌细胞的侵袭和迁移。MIR-142-3p在肝癌组织中的表达低于癌旁非癌组织,提示miR-142-3p具有抑癌作用。高迁移率盒蛋白1(HMGB 1)是一种促进肝癌转移的癌基因。单用MIR-142-3p或HMGB 1基因敲除可抑制肝癌细胞的侵袭和迁移,而HMGB 1过表达则阻碍miR-142-3p的作用。进一步的研究表明,HMGB 1是肝癌miR-142-3p的直接靶基因。MIR-142-3p通过直接结合HMGB 1的3‘非翻译区(UTR)来抑制HMGB 1基因的转录,从而抑制癌细胞的侵袭和迁移。结论:本研究首次报道miR-142-3p是一种通过直接调控HMGB 1基因转录而抑制肝癌细胞侵袭和迁移的新型抑癌基因。因此,miR-142-3p可能是肝癌患者潜在的诊断和治疗生物标志物。
关键词: 肝细胞癌,miR-142-3p,HMGB 1,迁移,侵袭,抑癌。
Current Molecular Medicine
Title:miR-142-3p Inhibits the Metastasis of Hepatocellular Carcinoma Cells by Regulating HMGB1 Gene Expression
Volume: 18 Issue: 3
关键词: 肝细胞癌,miR-142-3p,HMGB 1,迁移,侵袭,抑癌。
摘要: Background: Non-coding small RNAs are involved in organism development, and their aberrant regulation induces various diseases, including hepatocellular carcinoma (HCC), but their exact mechanisms have not been determined.
Objective: The aim was to investigate the role of miR-142-3p on HMGB1 expression in hepatocellular carcinoma.
Methods: Expression levels of miR-142-3p in HCC tissues and cultured cells were measured by RT-PCR. The invasion and metastasis abilities of HepG2 cells according to Transwell migration and invasion assays, and protein expression was measured by western blotting.
Results: The present study reported that miR-142-3p promotes the invasion and migration of HCC cells. miR-142-3p levels are lower in HCC tissues than in adjacent non-cancerous tissues, suggesting a tumor suppressor role for miR-142-3p. Highmobility group box protein 1 (HMGB1) is an oncogene that promotes the metastasis of HCC. miR-142-3p or HMGB1 knockdown alone inhibits the invasion and migration of HCC cells, and HMGB1 overexpression impedes the effect of miR-142-3p. Further studies showed that HMGB1 is a direct target gene of miR-142-3p in HCC. miR-142-3p represses HMGB1 gene transcription by directly binding to the 3′ untranslated region (UTR) of HMGB1, thereby inhibiting cancer cell invasion and migration.
Conclusion: This study, for the first time, reports that miR-142-3p is a novel tumor suppressor that inhibits the invasion and migration of HCC cells by directly regulating gene transcription of HMGB1. Thus, miR-142-3p may be a potential diagnostic and therapeutic biomarker for HCC patients.
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Cite this article as:
miR-142-3p Inhibits the Metastasis of Hepatocellular Carcinoma Cells by Regulating HMGB1 Gene Expression, Current Molecular Medicine 2018; 18 (3) . https://dx.doi.org/10.2174/1566524018666180907161124
DOI https://dx.doi.org/10.2174/1566524018666180907161124 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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