Renal cell carcinoma is a common
neoplasia of the adult kidney that accounts for about 3% of adult
malignancies.
Clear cell renal carcinoma is the most frequent subtype of
kidney cancer and 20-40% of patients develop
metastases. The absence of appropriate
biomarkers complicates diagnosis and prognosis of this disease. In this regard, small noncoding RNAs (
microRNAs), which are mutated in several neoplastic diseases including kidney
carcinoma, may be optimal candidates as
biomarkers for diagnosis and prognosis of this kind of
cancer. Here we show that patients with clear cell kidney
carcinoma that express low levels of miR501-5p exhibited a good prognosis compared with patients with unchanged or high levels of this
microRNA. Consistently, in kidney
carcinoma cells the downregulation of miR501-5p induced an increased
caspase-3 activity, p53 expression as well as decreased mTOR activation, leading to stimulation of the apoptotic pathway. Conversely, miR501-5p upregulation enhanced the activity of mTOR and promoted both cell proliferation and survival. These biological processes occurred through p53 inactivation by
proteasome degradation in a mechanism involving MDM2-mediated p53 ubiquitination. Our results support a role for miR501-5p in balancing apoptosis and cell survival in
clear cell renal carcinoma. In particular, the downregulation of microRNA501-5p promotes a good prognosis, while its upregulation contributes to a poor prognosis, in particular, if associated with p53 and MDM2 overexpression and mTOR activation. Thus, the expression of miR501-5p is a possible
biomarker for the prognosis of
clear cell renal carcinoma.