Xu Xiaoyong, Song Feihong, Jiang Xinwei, Hong Han, Fei Qiang, Jin Zhengkang, Zhu Xiang, Dai Binghua, Yang Jiamei, Sui Chengjun, Xu Minhui
Department of Hepato-Pancreato-Biliary Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, People's Republic of China.
Department of Special Treatment and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, People's Republic of China.
Onco Targets Ther. 2020 May 29;13:4865-4876. doi: 10.2147/OTT.S244530. eCollection 2020.
Thousands of long non-coding RNAs (lncRNAs) have been functionally verified as crucial regulators of physiological processes and disease progressions, yet their roles in hepatocellular carcinoma (HCC) have not been clearly illuminated.
We analyzed the expression of lncRNA-SNHG14 in TCGA data via bioinformatic analysis and detected its expression in HCC specimens by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Loss-of-function experiments were used to study the biological function of SNHG14 in HCC cells. RT-qPCR, Western blotting and dual-luciferase reporter assay were carried out to investigate the molecular mechanism of SNHG14 in HCC.
The upregulation of lncRNA-SNHG14 was observed in HCC tissues compared with normal tissues via RT-qPCR and bioinformatic analysis of TCGA data. Silencing of SNHG14 inhibited cell proliferation and induced cell apoptosis in HCC cells. microRNA-217 (miR-217), the tumor-suppressive miRNA in HCC, was predicted and confirmed as a miRNA sponged by SNHG14 in HCC cells. Via downregulation of miR-217, SNHG14 increased the expression of several miR-217-related oncogenes and subsequently activated oncogene-related signaling pathways in HCC cells. In addition, inhibition of miR-217 reversed SNHG14 silencing induced decrease of cell proliferation and increase of cell apoptosis. Their association was verified in the published microarray dataset and the collected HCC samples.
In summary, SNHG14 is involved in the development of HCC via sponging miR-217 and it may be a biomarker for patients with HCC.
数千种长链非编码RNA(lncRNA)已被功能验证为生理过程和疾病进展的关键调节因子,但其在肝细胞癌(HCC)中的作用尚未明确阐明。
我们通过生物信息学分析在TCGA数据中分析lncRNA-SNHG14的表达,并通过逆转录定量聚合酶链反应(RT-qPCR)检测其在HCC标本中的表达。功能丧失实验用于研究SNHG14在HCC细胞中的生物学功能。进行RT-qPCR、蛋白质印迹和双荧光素酶报告基因检测以研究SNHG14在HCC中的分子机制。
通过RT-qPCR和TCGA数据的生物信息学分析,与正常组织相比,在HCC组织中观察到lncRNA-SNHG14上调。SNHG14的沉默抑制了HCC细胞的增殖并诱导细胞凋亡。微小RNA-217(miR-217)是HCC中的肿瘤抑制性微小RNA,被预测并证实为HCC细胞中被SNHG14吸附的微小RNA。通过下调miR-217,SNHG14增加了几种与miR-217相关的癌基因的表达,并随后激活了HCC细胞中癌基因相关的信号通路。此外,miR-217的抑制逆转了SNHG14沉默诱导的细胞增殖减少和细胞凋亡增加。它们的关联在已发表的微阵列数据集和收集的HCC样本中得到验证。
总之,SNHG14通过吸附miR-217参与HCC的发生发展,它可能是HCC患者的一个生物标志物。