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Everolimus resistance in clear cell renal cell carcinoma: miRNA-101 and HIF-2α as molecular triggers?

Aim: The majority of clear cell renal cell carcinoma patients develop resistance to mTOR inhibitors. Materials & methods: As an in vitro model four cell lines were used: HKC-8, 786- O, RCC-FG-2 and an everolimus-resistant cell line (786-OR) established during this study. The quantification of miRNA-101 and HIF-2α mRNA levels was assessed by real-time PCR. Results: We observed a significant decrease of miRNA-101 intracellular levels in 786-OR. However, this miRNA presented higher extracellular levels. Additionally, we found a significant increase of HIF-2α in 786-OR. Conclusion: The circulating levels of miRNA-101 may be a potential biomarker of anti-mTOR therapy response and resistance prediction. Moreover, the resistance to mTOR inhibitors seems to be related with the overexpression of HIF-2α.