Fu Yanchao, Li BingBing, Huang Renzheng, Ji Xia, Bai Wen-Kun
Department of Gastroenterology, The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China.
Department of Gastroenterology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, China.
Pathol Res Pract. 2022 Oct;238:154078. doi: 10.1016/j.prp.2022.154078. Epub 2022 Aug 13.
Increasing data indicate that long noncoding RNA (lncRNA) DLEU2 is implicated in carcinogenesis in multiple malignancies including hepatocellular carcinoma (HCC). However, the role and molecular mechanism by which lncRNA DLEU2 contributes to HCC remain unknown. The association of lncRNA DLEU2 with clinicopathological characteristics and prognosis in patients with HCC was analyzed by qRT-PCR, and public TCGA dataset. CCK-8, colony formation and Transwell assays were performed to verify the role of lncRNA DLEU2 in HCC. RNA immunoprecipitation (RIP), luciferase gene report and qRT-PCR assays were employed to uncover lncRNA DLEU2-spevific binding with miR-30a-5p. The effect of lncRNA DLEU2 and (or) miR-30a-5p on PTP4A1 expression was examined by Western blot analysis. As a consequence, we found that lncRNA DLEU2 was upregulated in HCC tissue samples and associated with distant metastasis and poor survival in patients with HCC. Knockdown of lncRNA DLEU2 impaired HCC cell proliferation, colony formation and invasion, but ectopic expression of lncRNA DLEU2 abolished these effects. Furthermore, lncRNA DLEU2 harbored a negative correlation and specific binding with miR-30a-5p in HCC cells. Knockdown of lncRNA DLEU2 upregulated miR-30a-5p, but downregulated its target PTP4A1, and miR-30a-5p abrogated lncRNA DLEU2-induced tumor-promoting effects and PTP4A1 upregulation. Taken together, our findings demonstrate that lncRNA DLEU2 promotes growth and invasion of HCC cells by regulating miR-30a-5p/ PTP4A1 axis.
越来越多的数据表明，长链非编码RNA（lncRNA）DLEU2与包括肝细胞癌（HCC）在内的多种恶性肿瘤的致癌作用有关。然而，lncRNA DLEU2促进HCC发生发展的作用及分子机制仍不清楚。通过qRT-PCR和公共TCGA数据集分析lncRNA DLEU2与HCC患者临床病理特征及预后的相关性。进行CCK-8、集落形成和Transwell实验以验证lncRNA DLEU2在HCC中的作用。采用RNA免疫沉淀（RIP）、荧光素酶基因报告和qRT-PCR实验揭示lncRNA DLEU2与miR-30a-5p的特异性结合。通过蛋白质免疫印迹分析检测lncRNA DLEU2和（或）miR-30a-5p对PTP4A1表达的影响。结果发现，lncRNA DLEU2在HCC组织样本中上调，且与HCC患者的远处转移和不良预后相关。敲低lncRNA DLEU2可抑制HCC细胞增殖、集落形成和侵袭，但lncRNA DLEU2的异位表达可消除这些作用。此外，lncRNA DLEU2在HCC细胞中与miR-30a-5p呈负相关且存在特异性结合。敲低lncRNA DLEU2可上调miR-30a-5p，但下调其靶标PTP4A1，而miR-30a-5p可消除lncRNA DLEU2诱导的肿瘤促进作用及PTP4A1上调。综上所述，我们的研究结果表明lncRNA DLEU2通过调控miR-30a-5p/PTP4A1轴促进HCC细胞的生长和侵袭。
