Cancer Biomark. 2019;26(1):79-91. doi: 10.3233/CBM-190142.
Non-small cell lung cancer (NSCLC) , as the most prevalent type of lung carcinoma with high severity, is of urgent necessity to be investigated for novel therapeutic strategies. Long non-coding RNAs (lncRNAs) are notable for their participation in cancer regulation, and lncRNA long intergenic non-protein coding RNA 641 (LINC00641) has been found to have an inhibitory influence on bladder cancer, but its role in NSCLC has not yet been studied. In this research, we launched an investigation into the biological functions and the underlying molecular mechanisms of LINC00641 in NSCLC. At first, downregulation of LINC00641 was identified in NSCLC cells. Functionally, LINC00641 suppressed cell proliferation and induced cell apoptosis in NSCLC, indicating that LINC00641 exerted tumor-suppressive role in NSCLC. Through mechanism investigation, we determined that LINC00641 acted as a competing endogenous RNA (ceRNA) in NSCLC by sponging miR-424-5p to upregulate phospholipid scramblase (PLSCR4) expression. Further rescue assays indicated that miR-424-5p and PLSCR4 could reverse LINC00641-mediated cellular processes. Taken together, it is demonstrated in our study that LINC00641 can function as a tumor suppressor in NSCLC via a ceRNA network.
非小细胞肺癌（NSCLC）是最常见的肺癌类型，其严重程度较高，因此急需研究新的治疗策略。长非编码 RNA（lncRNA）在癌症调控中具有重要作用，lncRNA 长基因间非蛋白编码 RNA 641（LINC00641）已被发现对膀胱癌具有抑制作用，但它在 NSCLC 中的作用尚未被研究。在这项研究中，我们研究了 LINC00641 在 NSCLC 中的生物学功能和潜在分子机制。首先，我们在 NSCLC 细胞中发现 LINC00641 下调。功能上，LINC00641 抑制 NSCLC 细胞的增殖并诱导细胞凋亡，表明 LINC00641 在 NSCLC 中发挥肿瘤抑制作用。通过机制研究，我们确定 LINC00641 通过海绵吸附 miR-424-5p 在 NSCLC 中作为竞争性内源 RNA（ceRNA）发挥作用，从而上调磷脂 scramblase（PLSCR4）的表达。进一步的挽救实验表明，miR-424-5p 和 PLSCR4 可以逆转 LINC00641 介导的细胞过程。总之，我们的研究表明，LINC00641 可以通过 ceRNA 网络在 NSCLC 中发挥肿瘤抑制作用。
