Release of MicroRNA-Containing Vesicles Can Stimulate Angiogenesis and Metastasis in Renal Carcinoma

Renal cell carcinoma is a common form of urologic tumor, with low incidence but a high metastatic rate at diagnosis and high frequency of relapse. Renal cell carcinoma comprises a heterogeneous group of subtypes, classified according to their histopathological features and clinical behavior. Diagnostic approaches used to identify malignant tissue are based on immunohistochemical techniques. However, new molecular methods have been recently proposed for profiling and staging renal tumors based on their microRNA (miRNAs) expression. In fact, miRNAs have been shown to have abnormal levels in many cancers compared with their normal tissue counterparts. For this reason, along with the fact that they are present in biological fluids, miRNAs could serve as a useful diagnostic tool. Moreover, miRNAs may modify the translational profile of cells through direct degradation of their target mRNAs or by blocking their translation into functional proteins. The biological function of secretory miRNAs requires protection from extracellular degrading enzymes, which is achieved by envelopment of miRNAs within extracellular vesicles (EVs), which are subsequently secreted. EVs are a heterogeneous population of vesicles that includes shedding vesicles and exosomes, and are variable in size, composition, and releasing mechanisms. Following uptake, EVs are able to induce epigenetic modifications in target cells by the transfer of active proteins, lipids, RNA, and miRNAs. Therefore, through the transfer of selected miRNAs, tumor-released EVs may provide oncogenic signals to stromal cells. In particular, EVs released from renal carcinoma stem cells contain miRNAs that are potentially involved in triggering angiogenesis and metastasis.