Small non-coding RNA signature in kidney cancer: The role of MicroRNA as a biomarker in Renal Cell Carcinoma

Kidney cancer is the most common malignancy of the urinary tract, and the type of renal epithelium known as RCC has the highest incidence rate. Renal cell carcinoma or RCC is the ۹th and ۱۴th most common cancer in men and women, respectively, and the ۱۶th cause of cancer-related death worldwide. Recent advances have begun to clarify the physiological and pathological roles of non-coding RNAs (ncRNAs) in various diseases, including cancer. Among these, microRNAs (miRNAs) have been the most studied and have emerged as key players that are involved in the regulation of important growth regulatory pathways in cancer pathogenesis. MicroRNAs have shown potential as screening tools for various human malignancies, particularly RCC. With sizes of ۲۳ nucleotides, miRNAs act as antisense transcripts, decreasing target gene expression post-transcriptionally. Although their regulatory effects on target gene expression are not significant, the interactive network between miRNAs, target genes, and downstream effectors significantly impacts cellular function regulation. Two kinds of RNase III molecules, i.e., Drosha and Dicer proteins participate in the miRNA processing in the nuclear and cytoplasmic cellular compartments, respectively .These molecules are known to influence key aspects of the carcinogenic process, including sustained proliferative capacity, growth inhibitor evasion, apoptosis resistance, invasive and metastatic programs, and angiogenic enhancement. Quantitative RT-PCR, western blot, and bioinformatics methods were used to evaluate the expression of miR-۵۰۱-۳p in RCC cell lines and clinical tissues .Large-scale detection of miRNA sequences in human renal specimens has identified dysregulated miRNAs in ccRCC tumors, linked to poor patient survival. Experiments in a transgenic model of Xp۱۱ RCC showed higher amounts of miR-۲۰۴-۵p in urinary exosomes, indicating its role as a diagnostic marker for Xp۱۱ tRCC. The oncogenic function of numerous miRNAs has been proved in RCC cells. These oncomiRs have been shown to enhance cell proliferation and invasive features of RCC cells whilst decreasing apoptosis Notably some tumor suppressor genes such PTEN APC and MEG۳ have been identified as targets of oncomiRs such as miR-۳۰۱a miR-۱۹۳a-۳p miR-۲۲ miR-۶۷۱-۵p, and miR-۷, indicating a possible mechanism for their participation in the pathogenesis of RCC. Instead, tumor suppressor miRNAs which are down-regulated in RCC cells have potential roles in the activation of apoptotic pathways and arrestment of cell cycle transition. A number of these miRNAs target EMT-associated genes such as ZEB۱, Slug, HOTAIR, and HIF-۱α. Thus, their down-regulation is associated with the enhancement of EMT program. miRNAs are regarded as potential markers of different malignancies including RCC and regulate several cancer-related cellular functions such as apoptosis, survival, migration and angiogenesis. Taken together, miRNAs participate in the pathogenesis of RCC and response of patients to diverse therapeutic modalities and they can be used as biomarkers for cancer. In addition, researchers designed a novel material and a small molecule compound that could mediate the level of miRNAs and have anticancer effects in vivo. Hence, clinical trials using RNA therapies and liquid biopsy-based are currently beginning, and it is likely that within the next few years, the results of these trials will influence treatment of renal cancer.

کلیدواژه ها:

miRNA ، renal cell carcinoma ، Small non-coding RNA ، Quantitative RT-PCR ، biomarker