环状 RNA SLC3A2 通过海绵吸附 miR-490-3p 并调节 PPM1F 表达，在肝癌中发挥致癌因子的作用。
CircSLC3A2 functions as an oncogenic factor in hepatocellular carcinoma by sponging miR-490-3p and regulating PPM1F expression.
机构信息
The Fifth Department of Digestion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China.
出版信息
Mol Cancer. 2018 Nov 23;17(1):165. doi: 10.1186/s12943-018-0909-7.
BACKGROUND
Non-coding RNAs (ncRNAs) have been reported to participate in tumor progression by regulating gene expression. Previous studies showed that protein phosphatase Mg2/Mn2 dependent 1F (PPM1F) acts a dual role in cancer growth and metastasis. But, the underlying mechanisms by which ncRNAs regulate PPM1F expression in hepatocellular carcinoma (HCC) are poorly understood.
METHODS
The association between PPM1F or miR-490-3p expression and clinicopathological features and prognosis in patients with HCC was analyzed by TCGA RNA-sequencing data. CircSLC3A2 was identified to bind with miR-490-3p by bioinformatic analysis, and the binding sites between miR-490-3p and PPM1F or circSLC3A2 were confirmed by dual luciferase report and RNA immunoprecipitation (RIP) assays. The localization and clinical significance of miR-490-3p and circSLC3A2 in patients with HCC were investigated by fluorescence in situ hybridization (FISH). MTT, Agar, and Transwell assays were conducted to evaluate the effects of miR-490-3p or circSLC3A2 on cell proliferation and invasive potential.
RESULTS
The expression of PPM1F or miR-490-3p was associated with poor survival and tumor recurrence, and acted as an independent prognostic factor in patients with HCC. Re-expression of miR-490-3p inhibited HCC cell proliferation and invasion by targeting PPM1F, but its inhibitor reversed these effects. Moreover, circSLC3A2, predominantly localized in the cytoplasm, exhibited an oncogenic role by sponging miR-490-3p and regulating PPM1F expression, and harbored a positive correlation with poor survival in patients with HCC.
CONCLUSION
CircSLC3A2 acts as an oncogenic factor in HCC by sponging miR-490-3p and regulating PPM1F expression.
背景
非编码 RNA（ncRNAs）已被报道通过调节基因表达参与肿瘤进展。先前的研究表明，蛋白磷酸酶 Mg2+/Mn2+依赖性 1F（PPM1F）在癌症生长和转移中起双重作用。但是，ncRNAs 调节肝癌（HCC）中 PPM1F 表达的潜在机制尚不清楚。
方法
通过 TCGA RNA 测序数据分析 PPM1F 或 miR-490-3p 表达与 HCC 患者临床病理特征和预后的关系。通过生物信息学分析鉴定 circSLC3A2 与 miR-490-3p 结合，通过双荧光素酶报告和 RNA 免疫沉淀（RIP）实验验证 miR-490-3p 与 PPM1F 或 circSLC3A2 的结合位点。通过荧光原位杂交（FISH）检测 miR-490-3p 和 circSLC3A2 在 HCC 患者中的定位和临床意义。通过 MTT、Agar 和 Transwell 实验评估 miR-490-3p 或 circSLC3A2 对细胞增殖和侵袭潜能的影响。
结果
PPM1F 或 miR-490-3p 的表达与不良生存和肿瘤复发相关，并作为 HCC 患者的独立预后因素。miR-490-3p 的重新表达通过靶向 PPM1F 抑制 HCC 细胞增殖和侵袭，但其抑制剂逆转了这些作用。此外，circSLC3A2 主要定位于细胞质，通过海绵 miR-490-3p 并调节 PPM1F 表达发挥致癌作用，与 HCC 患者的不良生存呈正相关。
结论
circSLC3A2 通过海绵 miR-490-3p 并调节 PPM1F 表达在 HCC 中发挥致癌因子的作用。
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