Bao Han, Guo Chun-Guang, Qiu Peng-Cheng, Zhang Xin-Lei, Dong Qi, Wang Yu-Kun
Department of Pharmacy Administration and Drug Information, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Department of Second Hepatobiliary Surgery, The First People's Hospital of Xianyang City, Shaanxi 712000, P.R. China.
Oncol Lett. 2017 Sep;14(3):2831-2837. doi: 10.3892/ol.2017.6492. Epub 2017 Jun 30.
Long non-coding RNAs (lncRNAs) serve an important role in numerous human diseases, including cancer. Abnormal expression of lncRNAs has been associated with a number of tumor types; however, the underlying mechanisms through which lncRNA functions have yet to be elucidated. The present study primarily focuses on insulin-like growth factor 2 antisense 1 (Igf2as), a lncRNA reported to be differentially expressed in hepatocellular carcinoma (HCC). Reverse transcription-quantitative polymerase chain reaction analysis was used to determine the level of Igf2as in HCC cells and tissues. Flow cytometry was used to determine the level of cell apoptosis following Igf2as suppression and western blot analysis was used to identify altered protein expression levels. The results demonstrated that Igf2as was upregulated in HCC cells and tissues, and that the inhibition of Igf2as using a targeted small interfering RNA (si-Igf2as), significantly decreased cell proliferation and increased apoptosis. Western blot analysis identified that the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway was inhibited in cells transfected with si-Igf2as. In addition, cell migration was markedly reduced by the knockdown of Igf2as. These results suggest that lncRNA Igf2as may control hepatocellular progression primarily through the regulation of the ERK/MAPK signaling pathway.
长链非编码RNA(lncRNAs)在包括癌症在内的多种人类疾病中发挥重要作用。lncRNAs的异常表达与多种肿瘤类型相关;然而,lncRNA发挥功能的潜在机制尚未阐明。本研究主要聚焦于胰岛素样生长因子2反义RNA1(Igf2as),这是一种据报道在肝细胞癌(HCC)中差异表达的lncRNA。采用逆转录-定量聚合酶链反应分析来测定HCC细胞和组织中Igf2as的水平。运用流式细胞术来测定Igf2as抑制后细胞凋亡水平,并采用蛋白质印迹分析来鉴定蛋白表达水平的变化。结果表明,Igf2as在HCC细胞和组织中上调,并且使用靶向小干扰RNA(si-Igf2as)抑制Igf2as可显著降低细胞增殖并增加细胞凋亡。蛋白质印迹分析表明,在转染si-Igf2as的细胞中,细胞外信号调节激酶/丝裂原活化蛋白激酶(ERK/MAPK)信号通路受到抑制。此外,敲低Igf2as可显著减少细胞迁移。这些结果表明,lncRNA Igf2as可能主要通过调节ERK/MAPK信号通路来控制肝细胞癌进展。