microRNA-520f inhibits hepatocellular carcinoma cell proliferation and invasion by targeting TM4SF1
microRNA-520f inhibits hepatocellular carcinoma cell proliferation and invasion by targeting TM4SF1
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DOI：
10.1016/j.gene.2018.03.003
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发表时间：
2018-05-30
期刊：
影响因子：
3.5
通讯作者：
Chen, Yunru
中科院分区：
文献类型：
--
作者：
Du, Xiaoqin;Fan, Wanhu;Chen, Yunru
microRNAs（miRNAs）在肿瘤发生中起着重要作用。miR-520 f的失调已经被暗示参与几种癌症进展。然而，miR 520 f在肝细胞癌（HCC）中的生物学功能尚不清楚。因此，本研究探讨了miR-520 f影响肝癌发展的分子机制。在这里，我们发现，与配对的正常组织和细胞系相比，miR-520 f在人HCC样品和细胞系中显著下调，如通过qRT-PCR检测的。此外，下调的miR-520 f与HCC患者中较大的肿瘤大小、晚期TNM分期和转移密切相关。MTT法、集落形成法、transwell法和流式细胞仪检测结果显示，miR-520 f过表达可显著抑制肝癌细胞的增殖、侵袭和迁移，使细胞周期阻滞于G 0/G1期，并促进细胞凋亡，而下调miR-520 f则表现出相反的作用。跨膜蛋白4 L-Six家族成员1（Transmembrane-4 L-Six family member-1，TM 4SF 1）被确定为miR-520 f的直接靶点，并且在HCC标本中发现miR-520 f和TM 4SF 1 mRNA水平之间呈负相关。修复实验表明，TM 4SF 1通过调节P13 K/AKT和p38 MAPK信号通路，部分抑制miR-520 f介导的肝癌细胞增殖和侵袭。结论：miR-520 f可能通过靶向TM 4SF 1抑制肝癌细胞的增殖和侵袭，为肝癌的治疗提供潜在的实验依据。
microRNAs (miRNAs) are reported to play crucial roles in tumorigenesis. Dysregulation of miR-520f has been implicated to be involved in several cancer progressions. However, the biological functions of miR520f in hepatocellular carcinoma (HCC) remain unclear. Thus, the molecular mechanism underlying miR-520f on HCC development was investigated in this study. Here, we found that miR-520f was remarkably down-regulated in human HCC samples and cell lines compared to paired normal tissues and cell lines as detected by qRT-PCR. Furthermore, the deregulated miR-520f was strongly associated with larger tumor size, advanced TNM stage, and metastasis in HCC patients. Functional investigations revealed that overexpression of miR-520f significantly suppressed cell proliferation, invasion and migration, caused cell cycle arrested at G0/G1 phase, and promoted cell apoptosis in HCC cells according to MTT, colony formation, transwell, and flow cytometry assays, respectively, whereas, downregulation of miR-520f exhibited inverse effects. Transmembrane-4 L-Six family member-1 (TM4SF1) was identified as a direct target of miR-520f, and an inverse relationship was found between miR-520f and TM4SF1 mRNA levels in HCC specimens. Rescue experiments suggested that restoration of TM4SF1 partially abolished miR-520f-meidated cell proliferation and invasion inhibition in HCC cells through regulating P13K/AKT and p38 MAPK signaling pathways. In conclusion, these data indicated that miR-520f acted as tumor suppressor in HCC proliferation and invasion by targeting TM4SF1, which might provide potential therapeutic evidence for HCC patients.