Meng Xiangrui, Deng Yanyao, He Shuhan, Niu Li, Zhu Hongwei
Department of Hepatopancreatobiliary Surgery, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.
Front Oncol. 2021 Feb 18;11:629947. doi: 10.3389/fonc.2021.629947. eCollection 2021.
The mortality and morbidity rates of pancreatic cancer (PC) have been increasing over the past two decades. Recent evidence indicates that long non-coding RNAs (lncRNAs) are usually dysregulated in the tumorigenesis and progression of PC. In the present study, we showed that the expression of LINC00857 was upregulated in PC and associated with poor prognosis based on the Gene Expression Profiling Interactive Analysis (GEPIA) database and validated in our PC tissues and cell lines. N-Methyladenosine (mA) was highly enriched within LINC00857 and enhanced its RNA stability. Knockdown of LINC00857 remarkably inhibited the proliferation and promoted the apoptosis of PC cells. Then, by using bioinformation analysis and verified experiments, we identified that LINC00857 functioned as a competing endogenous RNA (ceRNA) for sponging miR-150-5p, leading to the upregulation of its target E2F3 in PC cells. Taken above, our study revealed a potential ceRNA regulatory pathway in which LINC00857 modulates E2F3 expression by binding to miR-150-5p, ultimately promoting tumorigenesis in PC. LINC00857/miR-150-5p/E2F3 regulatory axis may be taken as an alternative therapeutic target for treating PC.
在过去二十年中，胰腺癌（PC）的死亡率和发病率一直在上升。最近的证据表明，长链非编码RNA（lncRNAs）在PC的肿瘤发生和进展过程中通常存在失调。在本研究中，基于基因表达谱交互分析（GEPIA）数据库，我们发现LINC00857在PC中表达上调且与不良预后相关，并在我们的PC组织和细胞系中得到验证。N6-甲基腺苷（mA）在LINC00857中高度富集并增强了其RNA稳定性。敲低LINC00857可显著抑制PC细胞的增殖并促进其凋亡。然后，通过生物信息学分析和验证实验，我们确定LINC00857作为竞争性内源RNA（ceRNA）发挥作用，通过海绵吸附miR-150-5p，导致其靶标E2F3在PC细胞中上调。综上所述，我们的研究揭示了一种潜在的ceRNA调控途径，其中LINC00857通过与miR-150-5p结合来调节E2F3表达，最终促进PC的肿瘤发生。LINC00857/miR-150-5p/E2F3调控轴可能作为治疗PC的替代治疗靶点。
