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miR-30d-5p 通过靶向 ATG5 抑制肾细胞癌的增殖和自噬。

miR-30d-5p suppresses proliferation and autophagy by targeting ATG5 in renal cell carcinoma.

机构信息

Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, China.

Medical College of Xi'an Jiao Tong University, China.

出版信息

FEBS Open Bio. 2021 Feb;11(2):529-540. doi: 10.1002/2211-5463.13025. Epub 2020 Dec 19.

Abstract

Previous reports have shown that miR-30d-5p functions as a tumor suppressor in prostate cancer and gallbladder carcinoma, but its role in renal cell carcinoma (RCC) remains elusive. This study was designed to explore the functional role of miR-30d-5p in proliferation and autophagy of RCC. Our results show that miR-30d-5p is significantly down-regulated in RCC tissues compared with normal tissues. miR-30d-5p overexpression suppressed cell proliferation, cell-cycle G1/S transition and autophagy, but promoted apoptosis in RCC cell lines (786-O and ACHN). Intriguingly, autophagy-related gene 5 (ATG5) was directly targeted by miR-30d-5p, as shown using luciferase reporter assay and biotin-avidin pull-down assay. Moreover, overexpression of ATG5 attenuated the inhibitory effect of miR-30d-5p on proliferation and autophagy in 786-O cells. These results suggest that miR-30d-5p suppresses proliferation and autophagy in RCC cells by targeting ATG5, and this pathway may be a suitable basis for the design of novel cancer therapeutics.

摘要

先前的报告表明,miR-30d-5p 在前列腺癌和胆囊癌中作为肿瘤抑制因子发挥作用,但它在肾细胞癌(RCC)中的作用仍不清楚。本研究旨在探讨 miR-30d-5p 在 RCC 增殖和自噬中的功能作用。我们的结果表明,miR-30d-5p 在 RCC 组织中明显低于正常组织。miR-30d-5p 的过表达抑制 RCC 细胞系(786-O 和 ACHN)中的细胞增殖、细胞周期 G1/S 过渡和自噬,但促进细胞凋亡。有趣的是,正如荧光素酶报告基因检测和生物素-亲和素下拉实验所显示的那样,自噬相关基因 5(ATG5)是 miR-30d-5p 的直接靶标。此外,ATG5 的过表达减弱了 miR-30d-5p 对 786-O 细胞增殖和自噬的抑制作用。这些结果表明,miR-30d-5p 通过靶向 ATG5 抑制 RCC 细胞的增殖和自噬,该途径可能为新型癌症治疗药物的设计提供合适的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a712/7876493/1ab5ba113e77/FEB4-11-529-g001.jpg

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