Molecular Mechanisms in Clear Cell Renal Cell Carcinoma: Role of miRNAs and Hypermethylated miRNA Genes in Crucial Oncogenic Pathways and Processes

Frontiers in Genetics

Alexey A. Dmitriev¹  Sergey G. Morozov²  Eleonora A. Braga²  Vitaly I. Loginov³  Marina V. Fridman⁴ 

[1] Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia;Institute of General Pathology and Pathophysiology, Moscow, Russia;Research Center of Medical Genetics, Moscow, Russia;Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia;

关键词: clear cell renal cell carcinoma;    microRNA;    target genes;    angiogenesis;    epithelial-mesenchymal transition;    metastasis;   

DOI  :  10.3389/fgene.2019.00320

来源: DOAJ

【 摘 要 】

Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer, and it has the highest mortality rate. The increasing drug resistance of metastatic ccRCC has resulted in the search for new biomarkers. Epigenetic regulatory mechanisms, such as genome-wide DNA methylation and inhibition of protein translation by interaction of microRNA (miRNA) with its target messenger RNA (mRNA), are deeply involved in the pathogenesis of human cancers, including ccRCC, and may be used in its diagnosis and prognosis. Here, we review oncogenic and oncosuppressive miRNAs, their putative target genes, and the crucial pathways they are involved in. The contradictory behavior of a number of miRNAs, such as suppressive and anti-metastatic miRNAs with oncogenic potential (for example, miR-99a, miR-106a, miR-125b, miR-144, miR-203, miR-378), is examined. miRNAs that contribute mostly to important pathways and processes in ccRCC, for instance, PI3K/AKT/mTOR, Wnt-β, histone modification, and chromatin remodeling, are discussed in detail. We also separately consider their participation in crucial oncogenic processes, such as hypoxia and angiogenesis, metastasis, and epithelial-mesenchymal transition (EMT). The review also considers the interactions of long non-coding RNAs (lncRNAs) and miRNAs of significance in ccRCC. Recent advances in the understanding of the role of hypermethylated miRNA genes in ccRCC and their usefulness as biomarkers are reviewed based on our own data and those available in the literature. Finally, new data and perspectives concerning the clinical applications of miRNAs in the diagnosis, prognosis, and treatment of ccRCC are discussed.

【 授权许可】

Unknown