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miR-148-3p 通过靶向 Bcl2 抑制胃癌细胞恶性表型和化疗耐药性。

miR-148-3p inhibits gastric cancer cell malignant phenotypes and chemotherapy resistance by targeting Bcl2.

机构信息

Department of Oncology, The Seventh Medical Center of Pla General Hospital, Beijing, China.

Department of General Surgery, The Seventh Medical Center of Pla General Hospital, Beijing, China.

出版信息

Bioengineered. 2024 Dec;15(1):2005742. doi: 10.1080/21655979.2021.2005742. Epub 2021 Nov 16.

Abstract

Gastric cancer (GC) is the fourth most common cancer in the world. This work was designed to explore the biological effects of miR-148-3p on GC. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was utilized t miR-148-3p in GC cell lines. The mimics and inhibitors of miR-148-3p were carefully transfected into GC cells to up-regulate or down-regulate miR-148-3p expression. Observe the effect on miR-148-3p expression change to GC cell proliferation, colony formation, tumorigenesis, chemotherapy sensitivity, transwell migration, and invasion. Use online database tool to predict the miR-148-3p promising targets, and can be verified via RT-qPCR, Western blot, and luciferase report. We found that miR-148-3p expression level in GC cells was markedly down-regulated ( < 0.05), as compared with human normal gastric mucosal cells GES-1. Otherwise, miR-148-3p overexpression could effectively inhibit the cell proliferation, cell cycle progress, colony formation, anti-apoptosis, anti-migration and anti-invasion in gastric cancer cells, whereas miR-148-3p inhibition exhibited the opposite phenomenon (P < 0.05). Further research revealed that Bcl2 set as a direct downstream target of miR-148-3p. Our study firstly confirmed that, miR-148-3p might play a crucial role in tumorigenesis, as well as development of gastric cancer by targeting Bcl2, and could become a promising target for gastric cancer treatment.

摘要

胃癌(GC)是世界上第四种最常见的癌症。本工作旨在探索 miR-148-3p 对 GC 的生物学效应。采用定量逆转录聚合酶链反应(RT-qPCR)检测 GC 细胞系中的 miR-148-3p。仔细转染 miR-148-3p 的模拟物和抑制剂,上调或下调 miR-148-3p 的表达。观察 miR-148-3p 表达变化对 GC 细胞增殖、集落形成、致瘤性、化疗敏感性、transwell 迁移和侵袭的影响。利用在线数据库工具预测 miR-148-3p 的潜在靶点,并通过 RT-qPCR、Western blot 和荧光素酶报告进行验证。我们发现,GC 细胞中的 miR-148-3p 表达水平明显下调(<0.05),与正常人胃黏膜细胞 GES-1 相比。相反,miR-148-3p 的过表达可有效抑制胃癌细胞的增殖、细胞周期进程、集落形成、抗凋亡、抗迁移和抗侵袭,而 miR-148-3p 的抑制则表现出相反的现象(P<0.05)。进一步研究表明,Bcl2 是 miR-148-3p 的直接下游靶标。本研究首次证实,miR-148-3p 通过靶向 Bcl2 在胃癌的发生和发展中可能发挥关键作用,并可能成为治疗胃癌的有前途的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/250a/10841002/b144a53b70e6/KBIE_A_2005742_F0001_OC.jpg

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