DARS-AS1 promotes clear cell renal cell carcinoma by sequestering miR-194-5p to up-regulate DARS.

ABSTRACT

Clear cell renal cell carcinoma (ccRCC), the most frequent subtype of renal cell carcinoma (RCC), is characterized by high relapse rate and mortality. Long non-coding RNAs (lncRNAs) are critical participants during cancer development. LncRNA DARS antisense RNA 1 (DARS-AS1), a newly-found lncRNA, is not specifically reported in ccRCC. However, Gene Expression Profiling Interactive Analysis (GEPIA) and starBase databases revealed the up-regulation of DARS-AS1 in ccRCC. Current study investigated the function and mechanism of DARS-AS1 in ccRCC. Functional assays including colony formation assay, EdU assay, caspase-3 activity detection, flow cytometry analysis and JC-1 assay were implemented to identify the role of DARS-AS1 in ccRCC. As a result, silencing of DARS-AS1 retarded proliferation and facilitated apoptosis in ccRCC cells. Moreover, mainly a cytoplasmic localization of lncRNA DARS-AS1 was verified in ccRCC cells. Then, we demonstrated that DARS-AS1 positively regulated its nearby gene, aspartyl-tRNA synthetase (DARS), by sequestering miR-194-5p. Moreover, DARS was testified as the oncogene in ccRCC and DARS-AS1 worked as a tumor-facilitator in ccRCC through miR-194-5p/DARS signaling. In a summary, this study firstly uncovered that DARS-AS1 boosted DARS expression via absorbing miR-194-5p, therefore contributing to malignancy in ccRCC. Our findings may be helpful for opening new strategies for ccRCC treatment.