miR-424-5p 通过靶向 TRIM29 作为潜在的生物标志物抑制肝癌的增殖和侵袭。

MicroRNA-424-5p acts as a potential biomarker and inhibits proliferation and invasion in hepatocellular carcinoma by targeting TRIM29.

机构信息

Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHFPC, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

出版信息

Life Sci. 2019 May 1;224:1-11. doi: 10.1016/j.lfs.2019.03.028. Epub 2019 Mar 12.

DOI:10.1016/j.lfs.2019.03.028

PMID:30876939

Abstract

BACKGROUND

miRNA-424-5p (miR-424-5p) has been implicated in the development and progression of various tumors. However, the functional mechanisms of miR-424-5p in hepatocellular carcinoma (HCC) are unclear. In this study, we investigated the specific biological functions of miRNA in HCC.

METHODS

The expression of miR-424-5p was measured by qRT-PCR in HCC tissues and cell lines. Western blot and immunohistochemistry were used to detect the protein expression level of TRIM29. The relationship between miR-424-5p and the clinicopathological features of HCC patients was analyzed. Cell function experiments were performed to examine proliferation and invasion in HCC cells. The miRNA database was used to predict downstream target genes of miR-424-5p, which were verified by a luciferase reporter assay. Furthermore, cell and animal experiments confirmed that miR-424-5p exerts its biological function through the target gene TRIM29.

RESULTS

miR-424-5p expression was decreased in HCC tissues and cell lines, and correlated with AFP, TNM stage, intrahepatic metastasis and poor overall survival in HCC. The upregulation of miR-424-5p inhibited cell proliferation and invasion in vitro and suppressed HCC tumor growth in vivo. TRIM29 was confirmed to be the downstream target gene of miR-424-5p. Finally, rescue experiments suggested that the upregulation of TRIM29 could rescue inhibitory effect of miR-424-5p overexpression on cell proliferation and migration.

CONCLUSION

miR-424-5p is a tumor suppressor miRNA that inhibits cell proliferation and invasion via directly modulating TRIM29, which is related to cell proliferation and invasion in HCC. Thus, miR-424-5p may be a potential therapeutic and new prognostic marker for HCC.

摘要

背景

miRNA-424-5p（miR-424-5p）已被牵涉到各种肿瘤的发展和进展中。然而，miR-424-5p 在肝细胞癌（HCC）中的功能机制尚不清楚。在本研究中，我们研究了 miRNA 在 HCC 中的特定生物学功能。

方法

通过 qRT-PCR 测量 HCC 组织和细胞系中 miR-424-5p 的表达。Western blot 和免疫组织化学用于检测 TRIM29 的蛋白表达水平。分析 miR-424-5p 与 HCC 患者临床病理特征的关系。进行细胞功能实验以检测 HCC 细胞的增殖和侵袭。使用 miRNA 数据库预测 miR-424-5p 的下游靶基因，并通过荧光素酶报告基因检测进行验证。此外，细胞和动物实验证实 miR-424-5p 通过靶基因 TRIM29 发挥其生物学功能。

结果

miR-424-5p 在 HCC 组织和细胞系中表达降低，与 AFP、TNM 分期、肝内转移和 HCC 患者的总体生存不良相关。miR-424-5p 的上调抑制了体外细胞增殖和侵袭，并抑制了体内 HCC 肿瘤的生长。TRIM29 被确认为 miR-424-5p 的下游靶基因。最后，挽救实验表明，TRIM29 的上调可以挽救 miR-424-5p 过表达对细胞增殖和迁移的抑制作用。