LINC00645 inhibits renal cell carcinoma progression by interacting with HNRNPA2B1 to regulate the ROCK1 mRNA stability

LINC00645 通过与 HNRNPA2B1 相互作用调节 ROCK1 mRNA 稳定性来抑制肾细胞癌进展

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作者:Hao Li, Xu Han, Liang Song, Xiang Li, Liwei Zhang, Zhibo Jin, Yu Zhang, Tao Wang, Zhenlin Huang, Zhankui Jia, Jinjian Yang

Abstract

The lncRNA plays an important role in tumorigenesis and the progression of renal cell carcinoma (RCC). LINC00645 is one of the most different expressed lncRNA between RCC and normal renal tissue. However, the regulatory mechanism of LINC00645 in RCC remains unknown. Our results indicated that LINC00645 inhibited RCC proliferation, migration, and invasion. Mechanistically, HNRNPA2B1 directly bound to ROCK1 mRNA and strengthened its stability. LINC00645 competitively bound to the RRM1 domain, which is responsible for interacting with ROCK1 mRNA, reducing ROCK1 mRNA level by affecting posttranscriptional destabilization. The expression of LINC00645 was significantly reduced in RCC cells, significantly upregulating ROCK1 by abolishing the interaction with HNRNPA2B1, finally promoting RCC proliferation, migration, and invasion. Moreover, RCC cells with lower LINC00645 expression were more sensitive to the ROCK1 inhibitor Y-27632. Our study indicates that decreased expression of LINC00645 promotes the RCC progression via HNRNPA2B1/ROCK1 axis, providing a promising treatment strategy for RCC patients with decreased LINC00645 expression.

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