Abstract
While the androgen receptor (AR) might promote renal cell carcinoma (RCC) initiation and progression, the molecular mechanisms involved remain largely unclear. Here, we discovered the novel LncRNA-SARCC, which was suppressed and associated with better prognosis in RCC. Preclinical studies using multiple RCC cells and in vivo mouse model indicated that LncRNA-SARCC could attenuate RCC cell invasion, migration and proliferation in vitro and in vivo. Mechanistically, LncRNA-SARCC bound and destabilized AR protein with an inhibition of AR function, which led to transcriptionally de-repress miR-143-3p expression, thus inhibition of its downstream signals including AKT, MMP-13, K-RAS and P-ERK. In addition, bisulfite sequencing analysis substantiated that LncRNA-SARCC promoter was highly methylated in renal cancer tissues compared with paired non-cancerous renal tissues. Notably, treating with Sunitinib, the multi-targeted receptor tyrosine kinase inhibitor, increased the expression of LncRNA-SARCC, which decreased RCC cells resistance to Sunitinib. Thus, our study presented a road map for targeting this newly identified LncRNA-SARCC and its pathway, which expands potential therapeutic strategies for RCC treatment.
Highlights
We reported that Long noncoding RNAs (LncRNAs)-SARCC functioned as a tumor suppressor in Renal cell carcinoma (RCC) through repressing androgen receptor (AR) activity by physical interaction
Expression of LncRNA-SARCC in ccRCC and metastatic ccRCC was reduced compared with that in surrounding non-tumor and non-metastatic tissues with a positive correlation ccRCC prognosis. These lower LncRNASARCC levels were associated with enhanced ccRCC invasion, migration, proliferation and resistance to Sunitinib therapy, via its regulation of AR that suppressed miR-143-3p expression to influence downstream genes such as K-RAS, MMP-13, AKT and P-ERK expression
Our report further substantiated the significance of AR in RCC by demonstrating that an interacting molecule such as LncRNASARCC functioning through AR could regulate RCC invasion, migration and proliferation both in vitro and in vivo
Summary
In a reciprocal manner, knocking down LncRNA-SARCC (shRNA-SARCC) in SW839 and OSRC-2 cells enhanced AR protein, but not mRNA expression as well as AR activity through luciferase reporter assay (Figures 1i and j).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
