Du Xiaoqin, Fan Wanhu, Chen Yunru
Department of Infectious Diseases, Weinan Center Hospital of Shaanxi Province, Weinan 714000, Shaanxi, China.
Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
Gene. 2018 May 30;657:30-38. doi: 10.1016/j.gene.2018.03.003. Epub 2018 Mar 2.
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.
据报道，微小RNA（miRNA）在肿瘤发生过程中发挥着关键作用。miR-520f的失调与多种癌症进展有关。然而，miR-520f在肝细胞癌（HCC）中的生物学功能仍不清楚。因此，本研究探讨了miR-520f在HCC发生发展中的分子机制。通过qRT-PCR检测，我们发现与配对的正常组织和细胞系相比，miR-520f在人类HCC样本和细胞系中显著下调。此外，失调的miR-520f与HCC患者更大的肿瘤大小、晚期TNM分期和转移密切相关。功能研究表明，根据MTT、集落形成、transwell和流式细胞术分析，miR-520f的过表达显著抑制了HCC细胞的增殖、侵袭和迁移，使细胞周期停滞在G0/G1期，并促进了细胞凋亡，而miR-520f的下调则表现出相反的效果。跨膜4 L-六家族成员1（TM4SF1）被鉴定为miR-520f的直接靶点，并且在HCC标本中发现miR-520f与TM4SF1 mRNA水平呈负相关。挽救实验表明，通过调节P13K/AKT和p38 MAPK信号通路，TM4SF1的恢复部分消除了miR-520f介导的HCC细胞增殖和侵袭抑制。总之，这些数据表明，miR-520f通过靶向TM4SF1在HCC增殖和侵袭中发挥肿瘤抑制作用，这可能为HCC患者提供潜在的治疗依据。
