Laboratory of Translational Medicine, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, 100853, China.
Department of Hepato-pancreato-biliary Surgery, Chinese PLA General Hospital, Beijing, 100853, China.
Biochem Biophys Res Commun. 2020 Dec 17;533(4):685-691. doi: 10.1016/j.bbrc.2020.10.061. Epub 2020 Nov 7.
Hepatocellular carcinoma (HCC) is a severe global health problem. There is increasing evidence for the important roles of long noncoding RNAs in tumorigenesis and metastasis in HCC. In this study, we identified and characterized a novel long noncoding RNA, LINC02580, involved in HCC. LINC02580 was highly downregulated in HCC cohorts and was identified as a tumor suppressor. Low LINC02580 expression in patients with HCC was correlated with poor prognosis. Functional assays indicated that LINC02580-deficient cells show enhanced colony formation, migration, and invasion in vitro and promote subcutaneous tumor formation and distant lung metastasis in vivo. With respect to the underlying mechanism, we found that LINC02580 modulates the epithelial-mesenchymal transition (EMT) associated pathway in HCC cells by specifically binding to serine and arginine-rich splicing factor 1 (SRSF1). In summary, our findings illustrated that LINC02580 is a metastasis-suppressing lncRNA in HCC, and provided vital clues of how LINC02580 performs its biological functions. Further, this lncRNA may be a potential target in the prognosis and treatment of HCC.
肝细胞癌 (HCC) 是一个严重的全球健康问题。越来越多的证据表明长非编码 RNA 在 HCC 的肿瘤发生和转移中起着重要作用。在这项研究中，我们鉴定并表征了一种新型长非编码 RNA，LINC02580，其参与 HCC 的发生。LINC02580 在 HCC 队列中高度下调，被鉴定为肿瘤抑制因子。HCC 患者中低表达 LINC02580 与预后不良相关。功能测定表明，LINC02580 缺陷细胞在体外表现出增强的集落形成、迁移和侵袭能力，并在体内促进皮下肿瘤形成和远处肺转移。关于潜在机制，我们发现 LINC02580 通过特异性结合丝氨酸/精氨酸丰富剪接因子 1 (SRSF1) 来调节 HCC 细胞中的上皮-间充质转化 (EMT) 相关途径。总之，我们的研究结果表明 LINC02580 是 HCC 中一种抑制转移的 lncRNA，为 LINC02580 发挥其生物学功能的机制提供了重要线索。此外，该 lncRNA 可能是 HCC 预后和治疗的潜在靶点。
