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TP73-AS1通过调控miR-27b-3p/TMED5轴促进胃癌的增殖和侵袭。

TP73-AS1 promotes gastric cancer proliferation and invasion by regulation miR-27b-3p/TMED5 axis.

作者信息

Bao Chenhui, Guo Lin

机构信息

Department of General surgery, ShengJing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang City, Liaoning Province, China 110004.

出版信息

J Cancer. 2022 Feb 7;13(4):1324-1335. doi: 10.7150/jca.66683. eCollection 2022.

DOI:10.7150/jca.66683
PMID:35281863
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8899379/
Abstract

Gastric cancer (GC) is a common gastrointestinal malignancy. Evidence suggests that long non-coding RNAs (lncRNAs) influence mRNA expression to induce GC progression. We aim to investigate the function and regulatory mechanism of TP73-AS1 in GC. We detected TP73-AS1, miR-27b-3p, and TMED5 (Transmembrane P24 Trafficking Protein 5) by real-time polymerase chain reaction (RT-PCR). Similarly, the protein levels of TMED5 and wnt/β-catenin were detected by western-blot. The colony formation and Cell-Counting Kit-8 (CCK-8) assay detected cell proliferation. Transwell and scrape assay tested cell migration and invasion. Dual-luciferase reporter assays confirmed directed binding targets. Tumor xenograft in nude mice checked the result . TP73-AS1 over-expressed in GC. Suppressed TP73-AS1 inhibited cell proliferation, migration, and invasion. However, down-regulated miR-27b-3p could reverse the effects of weakenTP73-AS1 on the progression of GC. Moreover, TMED5 was also up-regulated in GC. Both TP73-AS1 and TMED5 were the direct target of miR-27b-3p. Meanwhile, miR-27b-3p was a negative correlation with TP73-AS1 and TMED5. The TP73-AS1/miR-27b-3p/TMED5 axis regulate wnt/β-catenin pathway. TP73-AS1 promoted GC proliferation, migration, and invasion by sponging miR-27b-3p to regulate TMED5. TP73-AS1 was a potential onco-lncRNA in GC.

摘要

胃癌(GC)是一种常见的胃肠道恶性肿瘤。有证据表明,长链非编码RNA(lncRNAs)会影响mRNA表达,从而促使胃癌进展。我们旨在研究TP73-AS1在胃癌中的功能及调控机制。我们通过实时聚合酶链反应(RT-PCR)检测TP73-AS1、miR-27b-3p和跨膜P24转运蛋白5(TMED5)。同样,通过蛋白质免疫印迹法检测TMED5和wnt/β-连环蛋白的蛋白水平。集落形成实验和细胞计数试剂盒-8(CCK-8)实验检测细胞增殖情况。Transwell实验和划痕实验检测细胞迁移和侵袭能力。双荧光素酶报告基因实验确定直接的结合靶点。通过裸鼠肿瘤异种移植实验验证结果。TP73-AS1在胃癌中过表达。抑制TP73-AS1可抑制细胞增殖、迁移和侵袭。然而,下调miR-27b-3p可逆转减弱的TP73-AS1对胃癌进展的影响。此外,TMED5在胃癌中也上调。TP73-AS1和TMED5均是miR-27b-3p的直接靶点。同时,miR-27b-3p与TP73-AS1和TMED5呈负相关。TP73-AS1/miR-27b-3p/TMED5轴调节wnt/β-连环蛋白通路。TP73-AS1通过海绵吸附miR-27b-3p来调节TMED5,从而促进胃癌的增殖、迁移和侵袭。TP73-AS1是胃癌中一种潜在的致癌lncRNA。

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