Abstract
MicroRNAs (miRs) are small noncoding RNAs that govern many biological processes. They frequently acquire a gain or a loss of function in cancer and hence play a causative role in the development and progression of neoplasms. They could be used as biomarkers to improve our knowledge on diagnosis, prognosis and drug resistance, and to attempt therapeutic approaches in several types of cancer including clear cell renal cell carcinoma (ccRCC). ccRCC is the most predominant subtype of RCC that accounts for about 90% of all renal cancers. Since ccRCC is generally asymptomatic until very late, it is difficult to diagnose early. Moreover, in the absence of preventive treatments for metastatic ccRCC after surgical resection of the primary cancer, predictive prognostic biomarkers are needed in order to achieve appropriate therapies. Herein the role of miRs in the biology of ccRCC and the potential applications of these molecules are discussed. Moreover, future applications in the diagnostic and prognostic field, as well as their impact on drug response and therapeutic targets are also explored. Their use in clinical practice as molecular biomarkers alone, or in combination with other biological markers could accelerate progress, help design personalized therapies, limit side effects, and improve quality of life of ccRCC patients.
Highlights
Renal cell carcinoma (RCC) accounts for 23% of all cancers and is the most common kidney malignancy with the highest mortality rate of urinary cancers
It is well known that the von Hippel-Lindau (VHL) gene, localized on chromosome 3p, is frequently inactivated either by mutation or methylation in over 80% of clear cell renal cell carcinoma (ccRCC) patients
The expression of miR-30a may affect autophagy in kidney cancer. It acts as an onco-suppressing agent and inhibits autophagy by targeting the BECN1 gene that codes for beclin-1, a protein crucial for the formation of the autophagosome. This miR is significantly reduced in both human RCC tissues and cell lines, and its restoration causes the inhibition of autophagy by the reduction of beclin-1 protein and enhances sorafenib-induced cytotoxicity in different ccRCC cell lines [39]
Summary
Renal cell carcinoma (RCC) accounts for 23% of all cancers and is the most common kidney malignancy with the highest mortality rate of urinary cancers. It acts as an onco-suppressing agent and inhibits autophagy by targeting the BECN1 gene that codes for beclin-1, a protein crucial for the formation of the autophagosome This miR is significantly reduced in both human RCC tissues and cell lines, and its restoration causes the inhibition of autophagy by the reduction of beclin-1 protein and enhances sorafenib-induced cytotoxicity in different ccRCC cell lines [39]. The restoring of normal levels of onco-suppressor miRs or the degradation of onco-miRs by using specific anti-miR sequences could be an attractive therapeutic strategy for the treatment of metastatic ccRCC In this regard, the downregulation of the miR-200 family in different tumors is associated with cell migration, invasion, and metastasis by the increased expression of IL-8 and CXCL1 genes that promote angiogenesis. There is an urgent need for developing efficient transfection methods as well as targetspecific delivery systems to realize the full therapeutic potential of miRs [65]
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