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- Title
ADAMTS9-AS1 inhibits tumor growth and drug resistance in clear cell renal cell carcinoma via recruiting HuR to enhance ADAMTS9 mRNA stability.
- Authors
Zhao, Enyang; Geng, Bo; Tao, Ran; You, Bosen; Liu, Yunli; Hou, Wenbin; Wang, Wanhui; Wang, Changlin; Li, Xuedong
- Abstract
The lack of efficacious treatments for clear cell renal cell carcinoma (ccRCC) has led to a poor 5-year survival rate. Here, we found that the expression of ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9) antisense RNA 1 (ADAMTS9-AS1) is commonly decreased in ccRCC tissues. Decreased ADAMTS9-AS1 is associated with advanced stages and poor prognosis in ccRCC patients. Additionally, we found that promoter hypermethylation contributes to the suppression of ADAMTS9-AS1 expression in ccRCC that contained relatively low levels of ADAMTS9-AS1. Further functional studies demonstrated that ADAMTS9-AS1 inhibits cell growth and drug resistance through enhancing mRNA stability of ADAMTS9 in ccRCC. Mechanistically, ADAMTS9-AS1 directly bound to Human Antigen R (HuR). Then, the ADAMTS9-AS1-HuR complex was guided to the ADAMTS9 3'UTR through specific RNA–RNA interaction. Moreover, ADAMTS9-AS1 expression is positively correlated with ADAMTS9 expression in ccRCC tissues. In summary, our data not only highlight the important role of ADAMTS9-AS1 in ccRCC progression, but also reveal new regulatory mechanisms of ADAMTS9, which provides important insights into novel treatment strategies targeting ADAMTS9-AS1-HuR- ADAMTS9 axis in ccRCC.
- Subjects
RENAL cell carcinoma; DRUG resistance; TUMOR growth; GENE expression; ANTISENSE RNA; PEPTIDASE
- Publication
Cancer Nanotechnology (1868-6958), 2023, Vol 14, Issue 1, p1
- ISSN
1868-6958
- Publication type
Article
- DOI
10.1186/s12645-023-00210-w