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微小RNA-129-5p通过调控骨形态发生蛋白2基因促进肝细胞癌的增殖和转移。

MicroRNA-129-5p promotes proliferation and metastasis of hepatocellular carcinoma by regulating the BMP2 gene.

作者信息

Liu Zengyao, Sun Jiefei, Wang Xiaochun, Cao Zhenyuan

机构信息

Department of Intervention, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

Interventional Catheter Therapy Section Office, Zhaodong Renmin Hospital, Zhaodong, Heilongjiang 151100, P.R. China.

出版信息

Exp Ther Med. 2021 Mar;21(3):257. doi: 10.3892/etm.2021.9688. Epub 2021 Jan 25.

DOI:10.3892/etm.2021.9688
PMID:33603864
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7851647/
Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor that poses a serious threat to human health. Due to its occult onset and rapid development, HCC is a challenge to diagnose early and effectively treat, and thus patients with HCC often have an unfavorable prognosis. MicroRNA (miR)-129 and its target gene play an important role in the regulation of various diseases. Therefore, the aim of the present study was to investigate the role and mechanism of action for miR-129-5p in the development of HCC. Quantitative results of clinical samples analyzed using reverse transcription-quantitative PCR suggested that miR-129-5p had a significantly lower expression level in tumoral tissues compared with corresponding peritumoral tissues. Overexpression of miR-129-5p in HCC cells was performed using a transfection technique, followed by MTT, Transwell, invasion and wound healing assays to detect the effect of miR-129-5p on the cell cytotoxicity and metastasis of liver cancer . The downstream target gene of miR-129-5p, bone morphogenetic protein 2 (BMP2), was determined using a luciferase reporter assay. Overexpression of miR-129-5p played a vital role in decreasing cytotoxicity and promoting metastasis of HCC, which may be attributed to its inhibitory effect on the expression of its target gene, BMP2. In clinical samples, miR-129-5p expression levels were found to be negatively correlated with BMP2 and closely associated with HCC metastasis and infiltration. Collectively, the results suggested that miR-129-5p may contribute to proliferation and metastasis of HCC through its target gene, BMP2, and thus may be a potential novel therapeutic target for the treatment of HCC.

摘要

肝细胞癌(HCC)是一种对人类健康构成严重威胁的恶性肿瘤。由于其发病隐匿且发展迅速,HCC在早期诊断和有效治疗方面具有挑战性,因此HCC患者的预后往往不佳。微小RNA(miR)-129及其靶基因在各种疾病的调控中发挥着重要作用。因此,本研究的目的是探讨miR-129-5p在HCC发生发展中的作用及作用机制。使用逆转录-定量PCR分析临床样本的定量结果表明,与相应的癌旁组织相比,miR-129-5p在肿瘤组织中的表达水平显著降低。采用转染技术在HCC细胞中过表达miR-129-5p,随后进行MTT、Transwell、侵袭和伤口愈合试验,以检测miR-129-5p对肝癌细胞毒性和转移的影响。使用荧光素酶报告基因检测法确定miR-129-5p的下游靶基因骨形态发生蛋白2(BMP2)。miR-129-5p的过表达在降低HCC细胞毒性和促进转移方面起着至关重要的作用,这可能归因于其对靶基因BMP2表达的抑制作用。在临床样本中,发现miR-129-5p表达水平与BMP2呈负相关,且与HCC转移和浸润密切相关。总的来说,结果表明miR-129-5p可能通过其靶基因BMP2促进HCC的增殖和转移,因此可能是治疗HCC的潜在新型治疗靶点。

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