肌萎缩蛋白样 1 反义 RNA 1 通过海绵吸附 miR-181a-5p 并调节 PTEN/PI3K/AKT/mTOR 信号通路抑制前列腺癌细胞增殖、侵袭和迁移。
Muscleblind-like 1 antisense RNA 1 inhibits cell proliferation, invasion, and migration of prostate cancer by sponging miR-181a-5p and regulating PTEN/PI3K/AKT/mTOR signaling.
机构信息
Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Clinical Medicine, Luohe Medical College, Luohe, China.
出版信息
Bioengineered. 2021 Dec;12(1):803-814. doi: 10.1080/21655979.2021.1890383.
The present study aimed to investigate the role and underlying mechanisms of long non-coding RNA (lncRNA) muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) in the progression of Prostate cancer (PCa). MBNL1-AS1 and microRNA (miR)-181a-5p expression in PCa tissues and several human PCa cell lines were analyzed, respectively, using StarBasev3.0 project and RT-qPCR assay. After MBNL1-AS1 overexpression, cell proliferation, invasion and migration were, respectively, evaluated using CCK-8, colony formation, transwell and wound healing assays. Dual luciferase assay were used for analysis of the interactions among MBNL1-AS1, miR-181a-5p, and phosphatase and tensin homolog (PTEN). Subsequently, the expression of PTEN and proteins in PI3K/AKT/mTOR signaling was examined using western blot analysis after transfection with miR-181a-5p mimic. The rescue assays were performed to investigate the effects of MBNL1-AS1 and miR-181a-5p on the functions of PCa cells and the expression of PTEN/PI3K/AKT/mTOR signaling by co-transfection with MBNL1-AS1 plasmid and miR-181a-5p mimic. Results indicated that MBNL1-AS1 was conspicuously downregulated while miR-181a-5p upregulating in PCa tissues and cell lines. MBNL1-AS1 overexpression decreased the abilities of cell proliferation, invasion, and migration. Further study revealed that MBNL1-AS1 acted as a sponge for miR-181a-5p and positively regulated PTEN by a sponge effect. Additionally, rescue assays proved that the effect of MBNL1-AS1-upregulation on the proliferation, invasion, and migration of PCa cells was dependent on miR-181a-5p. Furthermore, miR-181a-5p overexpression counteracted the expression of PTEN and proteins in PI3K/AKT/mTOR signaling exerted by MBNL1-AS1-upregulation in PCa cells. This study suggests that MBNL1-AS1 inhibits the progression of PCa via sponging miR-181a-5p and regulating PTEN/PI3K/AKT/mTOR pathway.
本研究旨在探讨长链非编码 RNA (lncRNA) 肌营养不良蛋白样 1 反义 RNA 1 (MBNL1-AS1) 在前列腺癌 (PCa) 进展中的作用及其潜在机制。分别利用 StarBasev3.0 项目和 RT-qPCR 检测 PCa 组织和几种人前列腺癌细胞系中 MBNL1-AS1 和 microRNA (miR)-181a-5p 的表达。通过 CCK-8 法、集落形成实验、Transwell 实验和划痕愈合实验分别评估过表达 MBNL1-AS1 后细胞的增殖、侵袭和迁移能力。双荧光素酶报告基因实验分析 MBNL1-AS1、miR-181a-5p 与磷酸酶和张力蛋白同源物 (PTEN) 之间的相互作用。随后，转染 miR-181a-5p 模拟物后，通过 Western blot 分析检测 PI3K/AKT/mTOR 信号通路中 PTEN 和蛋白的表达。通过共转染 MBNL1-AS1 质粒和 miR-181a-5p 模拟物进行挽救实验，研究 MBNL1-AS1 和 miR-181a-5p 对 PCa 细胞功能和 PTEN/PI3K/AKT/mTOR 信号表达的影响。结果表明，MBNL1-AS1 在 PCa 组织和细胞系中明显下调，而 miR-181a-5p 上调。MBNL1-AS1 的过表达降低了细胞增殖、侵袭和迁移的能力。进一步研究表明，MBNL1-AS1 通过海绵效应作为 miR-181a-5p 的海绵，并通过海绵效应正向调节 PTEN。此外，挽救实验证明，MBNL1-AS1 上调对 PCa 细胞增殖、侵袭和迁移的影响依赖于 miR-181a-5p。此外，miR-181a-5p 的过表达逆转了 MBNL1-AS1 上调在 PCa 细胞中对 PI3K/AKT/mTOR 信号通路中 PTEN 和蛋白表达的影响。本研究表明，MBNL1-AS1 通过海绵吸附 miR-181a-5p 抑制 PCa 的进展，并调节 PTEN/PI3K/AKT/mTOR 通路。
Zotero 插件