Abstract
MicroRNAs (miRNAs) were reported to be involved in the development of clear cell renal cell carcinoma (ccRCC). However, the study on miRNAs in ccRCC is far from complete. The present study identified miRNAs which could act as potential novel prognostic markers for ccRCC, and analyzed its possible mechanism. We found that miR-19a correlated with poor prognosis of ccRCC patients via promoting cell proliferation and suppressing PTEN/SMAD4 expression. Both the microarray screening result and TCGA KIRC dataset analysis showed that miR-19a was significantly upregulated in ccRCC tissues, and further analysis of TCGA data revealed that the upregulated level of miR-19a was strongly associated with advanced T stage and poor prognosis of ccRCC patients. Consistent with clinical observations, miR-19a overexpression significantly promoted ccRCC cell proliferation invitro. To further explore the mechanism by which miR-19a correlated with cell proliferation and poor prognosis of ccRCC, we performed gene set enrichment analysis (GSEA) for target genes of miR-19a in ccRCC patients. Result indicated that the key target genes of miR-19a included SMAD4 and PTEN. In ccRCC tissues, expression levels of SMAD4 and PTEN were negatively correlated with expression level of miR-19a, revealing that miR-19a suppressed the expression of SMAD4 and PTEN in ccRCC patients. miR-19a overexpression significantly suppressed the expression of SMAD4 and PTEN invitro, further verifying that SMAD4 and PTEN were the target genes of miR-19a in ccRCC cells. Our results elucidated the tumor promoting role of miR-19a and established miR-19a as a potential novel prognostic marker for ccRCC.
Highlights
Renal cell carcinoma (RCC) is one of the most common and lethal renal types of cancer, reducing the life quality of patients and presenting as an important socioeconomic problem
Integrative analysis of miRNA microarray and The Cancer Genome Atlas (TCGA) data suggested that the expression level of miR-19a was significantly upregulated in Clear cell RCC (ccRCC) tissues. miR-19a, annotated with cell proliferation, was significantly correlated with T stage and could act as an independent prognostic marker for ccRCC. miR-19a may promote cell proliferation mainly via suppressing the expression of SMAD family member 4 (SMAD4)/PTEN in ccRCC
A previous study demonstrated that miR-19a was aberrantly expressed in malignant glottic lesions [25] and several types of tumors, including lung [26] and gastric cancer [27]. miR-19a was strongly associated with cancer invasion and metastasis, and poor prognosis of lung cancer patients [26]. miR-19a could strongly induce hepatoma cell proliferation and colony formation in vitro [28]. miR-19a exerts these functions by constitutively activating the NF-κB signaling pathway [29], PI3K/Akt or JAK/STAT signaling pathway [30,31]
Summary
Renal cell carcinoma (RCC) is one of the most common and lethal renal types of cancer, reducing the life quality of patients and presenting as an important socioeconomic problem. Clear cell RCC (ccRCC) is the most common subtype (70-80%) of RCC [2]. MicroRNAs (miRNAs), emerging as endogenous triggers of the RNA interference pathway, were abnormally expressed in multiple types of cancer playing a significant role in the carcinogenesis or prognosis prediction [3,4]. Xing T and He H: Epigenomics of clear cell renal cell carcinoma.
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