Zhan Yangyang, Zheng NanXin, Teng Fei, Bao Leilei, Liu Fang, Zhang Mingjian, Guo Meng, Guo Wenyuan, Ding Guoshan, Wang Quanxing
Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China.
Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Oncotarget. 2017 May 22;8(40):67169-67180. doi: 10.18632/oncotarget.18052. eCollection 2017 Sep 15.
In this study, we explored the actions of miR-199a/b-5p during hepatocellular carcinoma (HCC) progression and its potential target genes. Through heatmap miRNA expression analysis of 15 matched HCC tumor and adjacent non-tumor liver tissues from the TCGA database, we detected 19 mRNAs that were upregulated and 13 that were downregulated specifically in HCC. Among these, miR-199 family members were downregulated in HCC tumors and cell lines, as compared to controls. Low miR-199a/b-5p expression was also associated with poor overall survival of HCC patients. miR-199a/b-5p overexpression in HCC cell lines inhibited cell proliferation, migration and invasion, both and . In addition, miR199-a/b-5p post-transcriptionally suppressed Rho-associated coiled-coil kinase 1 (ROCK1). This in turn led to inhibition of ROCK1/MLC and PI3K/Akt signaling, which is necessary for HCC proliferation and metastasis. These results indicate that miR-199a/b acts as tumor suppressors in HCC and represent promising therapeutic targets.
在本研究中，我们探究了miR-199a/b-5p在肝细胞癌（HCC）进展过程中的作用及其潜在靶基因。通过对来自TCGA数据库的15对匹配的HCC肿瘤组织和相邻非肿瘤肝组织进行热图miRNA表达分析，我们检测到19种在HCC中特异性上调的mRNA和13种特异性下调的mRNA。其中，与对照相比，miR-199家族成员在HCC肿瘤和细胞系中表达下调。miR-199a/b-5p低表达也与HCC患者较差的总生存期相关。在HCC细胞系中过表达miR-199a/b-5p可抑制细胞增殖、迁移和侵袭。此外，miR-199a/b-5p在转录后抑制Rho相关卷曲螺旋激酶1（ROCK1）。这进而导致ROCK1/MLC和PI3K/Akt信号通路受到抑制，而这两条信号通路对于HCC的增殖和转移是必需的。这些结果表明，miR-199a/b在HCC中起肿瘤抑制作用，是很有前景的治疗靶点。
