Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, China.
Medical College of Xi'an Jiao Tong University, China.
FEBS Open Bio. 2021 Feb;11(2):529-540. doi: 10.1002/2211-5463.13025. Epub 2020 Dec 19.
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.
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。
