miR-142-3p Inhibits the Metastasis of Hepatocellular Carcinoma Cells by Regulating HMGB1 Gene Expression
miR-142-3p Inhibits the Metastasis of Hepatocellular Carcinoma Cells by Regulating HMGB1 Gene Expression
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miR-142-3p通过调节HMGB1基因表达抑制肝细胞癌细胞转移
DOI：
10.2174/1566524018666180907161124
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发表时间：
2018-01-01
影响因子：
2.5
通讯作者：
Fan, X-G
中科院分区：
文献类型：
--
作者：
Fu, Y.;Sun, L-Q;Fan, X-G
背景资料：目的：探讨miR-142 - 3 p对肝癌组织中HMGB 1表达的影响。结果：miR-142- 3 p促进肝癌细胞的侵袭和迁移。miR-142- 3 p在HCC组织中的水平低于邻近的非癌组织，表明miR-142- 3 p具有肿瘤抑制作用。高迁移率族蛋白1（HMGB 1）是一种促进肝癌转移的癌基因。miR-142- 3 p或HMGB 1单独敲低抑制HCC细胞的侵袭和迁移，HMGB 1过表达阻碍miR-142- 3 p的作用。进一步的研究表明，HMGB 1是miR-142- 3 p在HCC中的直接靶基因。结论：本研究首次报道了miR-142 - 3 p是一种新的肿瘤抑制因子，它通过直接调控HMGB 1基因的转录而抑制肝癌细胞的侵袭和迁移。因此，miR-142- 3 p可能是HCC患者的潜在诊断和治疗生物标志物。
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. High-mobility 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.