MicroRNA-301a-3p suppressed the progression of hepatocellular carcinoma via targeting VGLL4
MicroRNA-301a-3p suppressed the progression of hepatocellular carcinoma via targeting VGLL4
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DOI：
10.1016/j.prp.2018.09.008
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发表时间：
2018-12-01
影响因子：
2.8
通讯作者：
Xiong, Jianping
中科院分区：
文献类型：
--
作者：
Hu, Jinhua;Ruan, Jiugen;Xiong, Jianping
microRNAs（miRNAs）的失调参与了包括肿瘤发生在内的多种生物学过程。据报道，miR-301 a-3 p是各种类型癌症中的致癌miRNA，如乳腺癌、恶性黑色素瘤和胰腺癌。然而，miR-301 a-3 p在肝细胞癌（HCC）中的作用在很大程度上仍然不完整。在本研究中，我们发现miR-301 a-3 p在HCC组织和细胞系中上调，较高的miR-301 a-3 p表达预示HCC患者预后不良。我们还证实了miR-301 a-3 p过表达增强了HCC细胞系的增殖、侵袭和化疗耐药能力，相反，沉默miR-301 a-3 p表达诱导了相反的效果。VGLL 4是miR-301 a-3 p的直接靶点，通过生物信息学网站预测，并通过western blot、RT-PCR和荧光素酶报告基因分析得到证实。增强的VGLL 4表达挽救了miR-301 a-3 p模拟物对细胞增殖、侵袭和化学抗性的作用。此外，我们发现miR-301 a-3 p调节TEAD的转录活性。总的来说，我们的研究结果表明，miR-301 a-3 p-VGLL 4信号轴可能是HCC的潜在治疗靶点。
Dysregulation of microRNAs (miRNAs) is involved in a variety of biological process including tumorigenesis. miR-301a-3p has been reported to be an onco-miRNA in various types of cancer, like breast cancer, malignant melanoma, and pancreatic cancer. However, the role of miR-301a-3p in hepatocellular carcinoma (HCC) remains largely incomplete. In the present study, we found that miR-301a-3p was upregulated in HCC tissues and cell lines, and higher miR-301a-3p expression predicted poor prognosis in HCC patients. We also demonstrated that miR-301a-3p overexpression enhanced the ability of proliferation, invasion, and chemoresistance in HCC cell lines, and conversely, silencing miR-301a-3p expression induced the opposite effects. VGLL4, as the direct target of miR-301a-3p, was predicted by bioinformatic websites and confirmed by western blot, RT-PCR, and luciferase reporter assay. Enforced VGLL4 expression rescued the effects of miR-301a-3p mimics on cell proliferation, invasion and chemoresistance. Moreover, we found miR-301a-3p modulated the transcription activity of TEADs. Collectively, our findings suggested that the miR-301a-3p-VGLL4 signaling axis might be a potential therapeutic target for HCC.