ADAMTS9-AS1 inhibits tumor growth and drug resistance in clear cell renal cell carcinoma via recruiting HuR to enhance ADAMTS9 mRNA stability

作者：Zhao, Enyang; Geng, Bo; Tao, Ran; You, Bosen; Liu, Yunli; Hou, Wenbin; Wang, Wanhui; Wang, Changlin^*; Li, Xuedong^*

来源：Cancer Nanotechnology, 2023, 14(1): 57.

DOI：10.1186/s12645-023-00210-w

• ADAMTS9-AS1
• ADAMTS9
• HuR
• ccRCC
• Cell growth

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.

• 单位
  哈尔滨医科大学