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RBM10的下调通过miR-224-5p/RBM10/p53反馈环促进肺腺癌的增殖和转移。

Down regulation of RBM10 promotes proliferation and metastasis via miR-224-5p/RBM10/p53 feedback loop in lung adenocarcinoma.

作者信息

Sun Xi, Jia Dexin, Yu Yan

机构信息

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.

出版信息

Heliyon. 2024 Jul 22;10(15):e35001. doi: 10.1016/j.heliyon.2024.e35001. eCollection 2024 Aug 15.

Abstract

RNA-binding motif protein 10 (RBM10) has a tumor suppressor role in multiple cancers. Combining Oncomine database results with tissue samples, Western blot analysis showed that RBM10 was significantly lower in lung adenocarcinoma (LUAD) than in adjacent normal tissues. Moreover, KM analysis revealed that the group with higher RBM10 expression in LUAD correlated with better overall survival (OS). Luciferase reporter assay revealed that an important tumor-promotive miRNA, miR-224-5p, was directly bound to the 3'UTR of RBM10, resulting in inhibition of RBM10 expression, and promoted LUAD progression both in vitro and in vivo. Mechanistically, we found that miR-224-5p directly targeted RBM10 to inhibit p53 expression during LUAD progression. Meanwhile, p53 affected RBM10 expression through p53/miR-224-5p axis. Our study identified RBM10 as a key tumor suppressor in the proliferation and metastasis of LUAD. The findings provide a novel mechanism involving a feedback loop of miR-224-5p/RBM10/p53 regulated tumor progression in LUAD, which may help with the design of more effective LUAD treatments.

摘要

RNA结合基序蛋白10(RBM10)在多种癌症中发挥肿瘤抑制作用。将Oncomine数据库结果与组织样本相结合,蛋白质免疫印迹分析显示,肺腺癌(LUAD)中的RBM10显著低于相邻正常组织。此外,Kaplan-Meier分析显示,LUAD中RBM10表达较高的组与更好的总生存期(OS)相关。荧光素酶报告基因检测显示,一种重要的促肿瘤微小RNA,即miR-224-5p,直接与RBM10的3'非翻译区(3'UTR)结合,导致RBM10表达受到抑制,并在体外和体内促进LUAD进展。机制上,我们发现miR-224-5p在LUAD进展过程中直接靶向RBM10以抑制p53表达。同时,p53通过p53/miR-224-5p轴影响RBM10表达。我们的研究确定RBM10是LUAD增殖和转移中的关键肿瘤抑制因子。这些发现提供了一种涉及miR-224-5p/RBM10/p53反馈环调节LUAD肿瘤进展的新机制,这可能有助于设计更有效的LUAD治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e2e/11320444/a594f75a30e0/gr1.jpg

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