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长链非编码RNA-MCEI通过miR-6759-5p介导食管鳞状细胞癌的化学敏感性，以竞争性调控胰岛素样生长因子2。

Lnc-MCEI mediated the chemosensitivity of esophageal squamous cell carcinoma via miR-6759-5p to competitively regulate IGF2.

作者信息

Liu Guangming, Guo Wei, Chen Guang, Li Wencan, Cui Youbin, Qin Junjie, Peng Jing

机构信息

Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, P.R. China.

Department of Hemotology, The First Hospital of Jilin University, Changchun 130021, P.R. China.

出版信息

Int J Biol Sci. 2020 Sep 16;16(15):2938-2950. doi: 10.7150/ijbs.47051. eCollection 2020.

DOI:10.7150/ijbs.47051
PMID:33061807
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7545712/
Abstract

Large amounts of long non-coding RNAs (lncRNAs) have been annotated whereas most of them have not been functionally characterized. Here we identified lncRNA ENST00000441932 as an oncogenic lncRNA in esophageal squamous cell carcinoma (ESCC) and named lnc-MCEI (lncRNA mediated the chemosensitivity of ESCC by regulating IGF2). What's more, the effect of lnc-MCEI on the chemosensitivity of ESCC was further evaluated. Bioinformatics analysis demonstrated that lnc-MCEI was involved in the tumorigenesis of ESCC and lnc-MCEI levels were significantly increased in ESCC cells and tissues. Additionally, lnc-MCEI knockdown retarded cell proliferation, colony formation of ESCC cells, but induced cell apoptosis. Moreover, lnc-MCEI knockdown significantly improved the chemosensitivity of ESCC to cisplatin (DDP) both and . Further mechanisms disclosed that lnc-MCEI functioned as a competing endogenous RNA (ceRNA) via sponging miR-6759-5p and IGF2 was a target of miR-6759-5p. Meanwhile, we found that IGF2 suppressed chemosensitivity of ESCC cells via PI3K/AKT pathway. These data suggested that lnc-MCEI was an oncogenic lncRNA and lnc-MCEI knockdown enhanced chemosensitivity of ESCC cells to cisplatin by targeting miR-6759-5p /IGF2/PI3K/AKT axis.

摘要

大量的长链非编码RNA（lncRNA）已被注释，然而其中大多数尚未进行功能表征。在此，我们将lncRNA ENST00000441932鉴定为食管鳞状细胞癌（ESCC）中的一种致癌lncRNA，并将其命名为lnc-MCEI（lncRNA通过调节IGF2介导ESCC的化疗敏感性）。此外，进一步评估了lnc-MCEI对ESCC化疗敏感性的影响。生物信息学分析表明，lnc-MCEI参与了ESCC的肿瘤发生，且lnc-MCEI水平在ESCC细胞和组织中显著升高。此外，敲低lnc-MCEI可抑制ESCC细胞的增殖、集落形成，但诱导细胞凋亡。而且，敲低lnc-MCEI显著提高了ESCC对顺铂（DDP）的化疗敏感性。进一步的机制揭示，lnc-MCEI作为一种竞争性内源性RNA（ceRNA），通过海绵吸附miR-6759-5p发挥作用，且IGF2是miR-6759-5p的靶标。同时，我们发现IGF2通过PI3K/AKT途径抑制ESCC细胞的化疗敏感性。这些数据表明，lnc-MCEI是一种致癌lncRNA，敲低lnc-MCEI通过靶向miR-6759-5p/IGF2/PI3K/AKT轴增强了ESCC细胞对顺铂的化疗敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdbf/7545712/3f7edeb76814/ijbsv16p2938g008.jpg
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