Li Yan, Wang Ying, Shen Xiabo, Han Xinghua
Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.
Front Pharmacol. 2019 Oct 17;10:1202. doi: 10.3389/fphar.2019.01202. eCollection 2019.
Hypermethylated in cancer 1 (HIC1) is continually decreased in breast cancer. However, the underlying molecular basis of the upstream regulation of HIC1 remains elusive. Here, we showed that HIC1 was downregulated in breast cancer tissues. Bioinformatics analysis identified that miR-128 might potentially target HIC1. HIC1 was proved as the target gene of miR-128 by overexpressing or knocking down miR-128. Additionally, we observed that HIC1 suppression by miR-128 increased cell invasion, proliferation, and reduced apoptosis. Lastly, we found that miR-128 accelerated tumor growth in xenograft mice by inhibiting HIC1. Altogether, this study presents the first evidence that miR-128 suppresses the expression of HIC1 to accelerate breast cancerogenesis.
癌症中高甲基化基因1(HIC1)在乳腺癌中持续降低。然而,HIC1上游调控的潜在分子基础仍不清楚。在此,我们表明HIC1在乳腺癌组织中表达下调。生物信息学分析确定miR-128可能潜在靶向HIC1。通过过表达或敲低miR-128,证明HIC1是miR-128的靶基因。此外,我们观察到miR-128抑制HIC1可增加细胞侵袭、增殖并减少细胞凋亡。最后,我们发现miR-128通过抑制HIC1促进异种移植小鼠的肿瘤生长。总之,本研究首次证明miR-128通过抑制HIC1表达来加速乳腺癌发生。