Department of Clinical Laboratory, Ming Zhou Hospital of Zhejiang University, Ningbo, China.
Eur Rev Med Pharmacol Sci. 2019 Aug;23(16):6888-6898. doi: 10.26355/eurrev_201908_18728.
Increasing evidence has suggested that microRNAs (miRNAs) played critical roles in cancer development by acting as a tumor suppressor or tumor-promoting genes. However, the role of microRNA-330-3p (miR-330-3p) in hepatocellular carcinoma (HCC) is still unknown. This study aimed to investigate the expression and role of miR-330-3p in hepatocarcinogenesis.
A total of 30 human hepatocellular carcinoma tissues and adjacent normal tissues were obtained from 30 hepatocellular carcinoma patients. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay was carried out to measure the expression of miR-330-3p in HCC tissues and cell lines. The relation between B-cell translocation gene 1 (BTG1) and miR-330-3p was predicted by TargetScan and confirmed by dual-luciferase reporter assay. Cell Counting Kit-8 (CCK-8), flow cytometry analysis, and transwell assay were used to determine cell viability, apoptosis, cell migration, and invasion, respectively. In addition, the mRNA and protein expression of Cyclin D1, Bcl-2, Bax, and matrix metalloproteinase (MMP)9 were detected using qRT-PCR and Western blotting.
We found that miR-330-3p expression was up-regulated in HCC tissues and cell lines. BTG1 was a direct target of miR-330-3p and it was down-regulated in HCC tissues and cell lines. Moreover, down-regulation of miR-330-3p suppressed HCCLM3 cell viability, migration, invasion, and enhanced cell apoptosis, while the tumor-suppressive effects were reversed by BTG1-siRNA. In addition, miR-330-3p inhibitor decreased the expression of Cyclin D1, Bcl-2, and MMP9 while enhanced the expression of Bax. Meanwhile, BTG1-siRNA led to the opposite effects.
The data suggested that miR-330-3p acted as a tumor gene in HCC by targeting BTG1 and it might be a potential therapeutic target for the HCC treatment.
越来越多的证据表明，微小 RNA（miRNA）通过作为肿瘤抑制因子或肿瘤促进基因在癌症发展中发挥关键作用。然而，miR-330-3p 在肝细胞癌（HCC）中的作用仍不清楚。本研究旨在探讨 miR-330-3p 在肝癌发生中的表达和作用。
从 30 例 HCC 患者中获得 30 个人肝癌组织和相邻正常组织。采用定量实时聚合酶链反应（qRT-PCR）检测 HCC 组织和细胞系中 miR-330-3p 的表达。通过 TargetScan 预测 B 细胞易位基因 1（BTG1）与 miR-330-3p 的关系，并通过双荧光素酶报告基因实验证实。细胞计数试剂盒-8（CCK-8）、流式细胞术分析和 Transwell 实验分别用于测定细胞活力、细胞凋亡、细胞迁移和侵袭。此外，使用 qRT-PCR 和 Western blot 检测细胞周期蛋白 D1（Cyclin D1）、B 细胞淋巴瘤-2（Bcl-2）、Bcl-2 相关 X 蛋白（Bax）和基质金属蛋白酶（MMP）9 的 mRNA 和蛋白表达。
我们发现 miR-330-3p 在 HCC 组织和细胞系中表达上调。BTG1 是 miR-330-3p 的直接靶基因，在 HCC 组织和细胞系中表达下调。此外，下调 miR-330-3p 抑制 HCCLM3 细胞活力、迁移和侵袭，并增强细胞凋亡，而 BTG1-siRNA 则逆转了这些肿瘤抑制作用。此外，miR-330-3p 抑制剂降低了 Cyclin D1、Bcl-2 和 MMP9 的表达，同时增强了 Bax 的表达。同时，BTG1-siRNA 则导致相反的效果。
数据表明，miR-330-3p 通过靶向 BTG1 作为 HCC 的肿瘤基因发挥作用，它可能是 HCC 治疗的潜在治疗靶点。
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