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

• Published in: Gene Vol. 905; p. 148232
• Main Authors: Li, Hao, Han, Xu, Song, Liang, Li, Xiang, Zhang, Liwei, Jin, Zhibo, Zhang, Yu, Wang, Tao, Huang, Zhenlin, Jia, Zhankui, Yang, Jinjian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.05.2024
• Subjects: Carcinoma, Renal Cell - metabolism; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Gene Expression Regulation, Neoplastic; HNRNPA2B1; Humans; Kidney Neoplasms - pathology; LINC00645; Renal cell carcinoma; rho-Associated Kinases - genetics; RNA Stability; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Messenger - genetics; ROCK1; lncRNA; ROCK1; MS; qRT-PCR; DAPI; WB; DEGs; RCC; Renal cell carcinoma; NC; FBS; HNRNPA2B1; RIP; LINC00645; PCR
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2024.148232

•Low LINC00645 expression was associated with a high malignancy degree of RCC patients.•LINC00645 inhibited RCC cell proliferation, migration and invasion.•LINC00645 regulated ROCK1 expression by competitively binding to HNRNPA2B1 thus abolishing its protection of ROCK1 mRNA stability.•RCC with lower LINC00645 expression is more sensitive to ROCK1 inhibitors. 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.