Lou Weiyang, Chen Jing, Ding Bisha, Fan Weimin
Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, China.
Department of Oncology, First Affiliated Hospital of Jiaxing University, Jiaxing, 314000 Zhejiang, China.
Genomics. 2021 May;113(3):933-945. doi: 10.1016/j.ygeno.2021.02.003. Epub 2021 Feb 12.
MicroRNAs (miRNAs) are frequently aberrantly expressed in hepatocellular carcinoma (HCC) and are involved in its development. However, their role and mechanism in HCC are still not fully elucidated. Differential expression analysis and survival analysis were performed to identify potential miRNAs in HCC and miR-3607 was identified as a candidate therapeutic target and prognostic biomarker. RT-qPCR confirmed the low expression of mature miR-3607-3p and miR-3607-5p in HCC. Functional experiments suggested that both miR-3607-3p and miR-3607-5p significantly inhibited HCC proliferation and induced apoptosis. Next, the detailed mechanism of miR-3607-3p and miR-3607-5p in HCC was explored by combination of bioinformatic analysis and experimental validation, and uncovered that XIAP, a common target gene of miR-3607-3p and miR-3607-5p, was involoved in their tumor suppressive effects. Finally, a XIAP-associated protein-protein interaction network, consisting of 10 positively correlated genes, was established. Collectively, we for the first time suggest that miR-3607-3p and miR-3607-5p inhibit HCC by acting one common target XIAP.
微小RNA（miRNA）在肝细胞癌（HCC）中常出现异常表达，并参与其发展过程。然而，它们在HCC中的作用和机制仍未完全阐明。通过差异表达分析和生存分析来鉴定HCC中的潜在miRNA，miR-3607被确定为候选治疗靶点和预后生物标志物。逆转录定量聚合酶链反应（RT-qPCR）证实成熟的miR-3607-3p和miR-3607-5p在HCC中低表达。功能实验表明，miR-3607-3p和miR-3607-5p均能显著抑制HCC增殖并诱导凋亡。接下来，通过生物信息学分析与实验验证相结合的方式，探索miR-3607-3p和miR-3607-5p在HCC中的详细机制，发现XIAP作为miR-3607-3p和miR-3607-5p的共同靶基因，参与了它们的肿瘤抑制作用。最后，建立了一个由10个正相关基因组成的XIAP相关蛋白质-蛋白质相互作用网络。总体而言，我们首次表明miR-3607-3p和miR-3607-5p通过作用于共同靶点XIAP来抑制HCC。
