Potential tumor‑suppressive role of microRNA‑99a‑3p in sunitinib‑resistant renal cell carcinoma cells through the regulation of RRM2
Abstract
Sunitinib is the most common primary molecular‑targeted agent for metastatic clear cell renal cell carcinoma (ccRCC); however, intrinsic or acquired sunitinib resistance has become a significant problem in medical practice. The present study focused on microRNA (miR)‑99a‑3p, which was significantly downregulated in clinical sunitinib‑resistant ccRCC tissues in previous screening analyses, and investigated the molecular network associated with it. The expression levels of miR‑99a‑3p and its candidate target genes were evaluated in RCC cells, including previously established sunitinib‑resistant 786‑o (SU‑R‑786‑o) cells, and clinical ccRCC tissues, using reverse transcription‑quantitative polymerase chain reaction. Gain‑of‑function studies demonstrated that miR‑99a‑3p significantly suppressed cell proliferation and colony formation in RCC cells, including the SU‑R‑786‑o cells, by inducing apoptosis. Based on in silico analyses and RNA sequencing data, followed by luciferase reporter assays, ribonucleotide reductase regulatory subunit‑M2 (RRM2) was identified as a direct target of miR‑99a‑3p in the SU‑R‑786‑o cells. Loss‑of‑function studies using small interfering RNA against RRM2 revealed that cell proliferation and colony growth ...Continue Reading
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