Medical Experimental Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
Department of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
Oncol Rep. 2017 Jul;38(1):343-351. doi: 10.3892/or.2017.5702. Epub 2017 Jun 6.
Increasing evidence suggests that aberrant expression of certain microRNAs (miRNAs) may participate in the genesis and progression of tumors. Several studies have indicated that miR-1247-5p plays different roles in various types of cancer cells. The effects of miR-1247-5p on human hepatocellular carcinoma (HCC) cells are elusive. In the present study, we investigated the effects of miR-1247-5p on the progression of HCC. The transcript of miR-1247-5p was markedly downregulated in clinical samples of patients with HCC and HCC cell lines, and ectopic overexpression of miR‑1247-5p markedly inhibited the proliferation and invasion of HepG2 cells, induced cell apoptosis in vitro, and suppressed the growth of transplanted tumors in vivo. Wnt3 was found to be a potential target of miR-1247-5p and overexpression of miR-1247-5p was able to significantly downregulate the expression of Wnt3 by directly targeting the 3'UTR of this gene, which was verified by luciferase reporter assay and western blotting. Furthermore, we found that the miR-1247-5p gene was hypermethylated in HepG2 cells, and the transcript of miR-1247-5p was increased significantly after treatment with the demethylation drug 5-azacytidine. These findings demonstrated that miR-1247-5p functions as a tumor suppressor in human HCC by targeting Wnt3 and that the expression of miR-1247-5p can be regulated by DNA methylation, which indicates that miR-1247-5p has the potential to be a therapeutic target as well as a diagnostic marker of HCC.
越来越多的证据表明，某些 microRNAs（miRNAs）的异常表达可能参与肿瘤的发生和发展。有几项研究表明，miR-1247-5p 在不同类型的癌细胞中发挥不同的作用。miR-1247-5p 对人肝癌（HCC）细胞的影响尚不清楚。在本研究中，我们研究了 miR-1247-5p 对 HCC 进展的影响。miR-1247-5p 的转录物在 HCC 患者的临床样本和 HCC 细胞系中明显下调，miR-1247-5p 的异位过表达显著抑制 HepG2 细胞的增殖和侵袭，诱导体外细胞凋亡，并抑制体内移植瘤的生长。Wnt3 被发现是 miR-1247-5p 的一个潜在靶标，miR-1247-5p 的过表达能够通过直接靶向该基因的 3'UTR 显著下调 Wnt3 的表达，这通过荧光素酶报告基因检测和 Western blot 得到验证。此外，我们发现 miR-1247-5p 基因在 HepG2 细胞中呈高甲基化状态，用去甲基化药物 5-氮杂胞苷处理后，miR-1247-5p 的转录物显著增加。这些发现表明，miR-1247-5p 通过靶向 Wnt3 作为人 HCC 的肿瘤抑制因子发挥作用，miR-1247-5p 的表达可以通过 DNA 甲基化调节，这表明 miR-1247-5p 具有作为 HCC 治疗靶点和诊断标志物的潜力。
