Wang W, Lin H, Zhou L, Zhu Q, Gao S, Xie H, Liu Z, Xu Z, Wei J, Huang X, Zheng S
Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Lab of Organ Transplantation, Department of Hepatobilliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China.
Department of Vascular Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China.
Eur J Surg Oncol. 2014 Nov;40(11):1586-94. doi: 10.1016/j.ejso.2013.11.008. Epub 2013 Nov 19.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate physiological and pathological processes by suppressing target gene expression. Altered expression of miR-30a-3p has been demonstrated in several cancers. However, little about how miR-30a-3p functions in these cancers has been reported, and the role of miR-30a-3p in hepatocellular carcinoma (HCC) is unknown. The purpose of this study was to identify the role and underlying molecular mechanism of action of miR-30a-3p in HCC.
A total of 110 HCC patients, primarily treated by surgical removal of tumors, were involved in the study. HCC cell line Bel-7402 was selected to characterize the function of miR-30a-3p in vitro.
Our results showed that in 83.6% of the 110 HCC patients, expression of miR-30a-3p was significantly downregulated (P < 0.0001) in tumors compared to adjacent normal tissues. In a clinicopathological correlation analysis, downregulation of miR-30a-3p correlated with a significantly higher incidence of portal vein tumor thrombus (PVTT, P = 0.009). Moreover, miR-30a-3p markedly inhibited the invasion and migration of Bel-7402 HCC cells in vitro. Furthermore, miR-30a-3p overexpression had an inhibitory effect on cell proliferation, induced apoptosis and increased arrest of cells in the S phase. We further demonstrated that miR-30a-3p regulates HCC cell function by a mechanism involving reduced vimentin and MMP3 expression and restoration of E-cadherin expression.
our data suggest that miR-30a-3p is downregulated in HCC and acts as a tumor suppressor in vitro. Regulation of vimentin, E-cadherin and MMP3 by miR-30a-3p suggests a useful therapeutic strategy for tumors with reduced miR-30a-3p expression.
微小RNA(miRNA)是一类小的非编码RNA,通过抑制靶基因表达来调节生理和病理过程。在多种癌症中已证实miR-30a-3p的表达发生改变。然而,关于miR-30a-3p在这些癌症中的作用机制报道较少,其在肝细胞癌(HCC)中的作用尚不清楚。本研究旨在确定miR-30a-3p在HCC中的作用及潜在分子作用机制。
本研究共纳入110例主要接受手术切除肿瘤治疗的HCC患者。选择HCC细胞系Bel-7402在体外表征miR-30a-3p的功能。
我们的结果显示,在110例HCC患者中,83.6%的患者肿瘤组织中miR-30a-3p的表达与相邻正常组织相比显著下调(P < 0.0001)。在临床病理相关性分析中,miR-30a-3p的下调与门静脉癌栓(PVTT)的发生率显著升高相关(P = 0.009)。此外,miR-30a-3p在体外显著抑制Bel-7402 HCC细胞的侵袭和迁移。此外,miR-30a-3p过表达对细胞增殖有抑制作用,诱导细胞凋亡并增加细胞在S期的停滞。我们进一步证明,miR-30a-3p通过降低波形蛋白和MMP3表达以及恢复E-钙黏蛋白表达的机制来调节HCC细胞功能。
我们的数据表明,miR-30a-3p在HCC中表达下调,并在体外发挥肿瘤抑制作用。miR-30a-3p对波形蛋白、E-钙黏蛋白和MMP3的调节为miR-30a-3p表达降低的肿瘤提供了一种有用的治疗策略。