Department of Bile Duct Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
West China-Washington Mitochondria and Metabolism Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Biomed Pharmacother. 2020 Jun;126:110111. doi: 10.1016/j.biopha.2020.110111. Epub 2020 Mar 26.
Emerging evidence demonstrates that abnormally expressed long noncoding RNAs (lncRNAs) are involved in the progression of various cancers. However, the expression profiles and functions of lncRNAs in hepatocellular carcinoma (HCC) with microvascular invasion (MVI) remain largely unknown. In this study, we revealed the differential expression profiles of lncRNA and messenger RNA in four pairs of HCC with MVI and adjacent nontumor liver tissues by using high-throughput RNA sequencing. Among these dysregulated lncRNAs, lnc-TSPAN12 was the most significantly upregulated lncRNA in HCC. The results of real time-PCR showed that lnc-TSPAN12 was highly expressed in HCC, including HCC with MVI, and its high expression was associated with unfavorable clinicopathological features and poor prognosis. Moreover, multivariate Cox regression analysis verified that lnc-TSPAN12 was an independent prognostic predictor for overall and recurrence-free survival. Receiver operating characteristic curve analysis indicated that lnc-TSPAN12 could serve as a potential diagnostic biomarker for HCC with MVI. In addition, a loss-of-function experiment demonstrated that lnc-TSPAN12 knockdown inhibited HCC cell migration and invasion in vitro. Our findings suggest that lnc-TSPAN12 may function as an oncogene in HCC progression and could serve as a novel diagnostic/prognostic biomarker and potential therapeutic target for HCC with MVI.
越来越多的证据表明，异常表达的长链非编码 RNA（lncRNA）参与了多种癌症的进展。然而，lncRNA 在伴有微血管侵犯（MVI）的肝细胞癌（HCC）中的表达谱和功能仍知之甚少。在这项研究中，我们通过高通量 RNA 测序揭示了四对伴有 MVI 和相邻非肿瘤肝组织中 lncRNA 和信使 RNA 的差异表达谱。在这些失调的 lncRNA 中，lnc-TSPAN12 在 HCC 中表达最为显著上调。实时 PCR 结果表明，lnc-TSPAN12 在 HCC 中高表达，包括伴有 MVI 的 HCC，其高表达与不良的临床病理特征和预后不良相关。此外，多变量 Cox 回归分析证实 lnc-TSPAN12 是总生存期和无复发生存期的独立预后预测因子。受试者工作特征曲线分析表明，lnc-TSPAN12 可作为伴有 MVI 的 HCC 的潜在诊断生物标志物。此外，功能丧失实验表明，lnc-TSPAN12 敲低可抑制 HCC 细胞在体外的迁移和侵袭。我们的研究结果表明，lnc-TSPAN12 可能在 HCC 进展中作为癌基因发挥作用，可作为伴有 MVI 的 HCC 的新型诊断/预后生物标志物和潜在治疗靶点。
