The Role of HIF1-related Genes and Non-coding RNAs Expression in Clear Cell Renal Cell Carcinoma.

Abstract

Renal cell carcinoma is one of the three most common malignant urologic tumors, with clear cell renal cell carcinoma (ccRCC) representing its most common subtype. Although nephrectomy can radically cure the disease, a large percentage of patients is diagnosed when metastatic sites are present and thus alternative, pharmaceutical approaches need to be sought. Since HIF1 up-regulates the transcription of genes that range from metabolic enzymes to non-coding RNAs, and is a key molecule of ccRCC pathogenesis, this study aimed to investigate the expression ALDOA, SOX-6, and non-coding RNAs (mir-122, mir-1271, and MALAT-1) in samples from ccRCC patients. Tumor and adjacent normal tissue samples from 14 patients with ccRCC were harvested. Expression of ALDOA, mir-122, mir-1271, and MALAT-1 mRNA was estimated using real time PCR, whereas the expression of SOX-6 protein was investigated using immunohistochemistry. Up-regulation of HIF1 was observed, accompanied with up-regulation of ALDOA, MALAT-1, and mir-122. On the contrary, the expression of mir-1271 was found to be reduced, a finding that can be attributed to a potential MALAT-1 sponge function. Furthermore, SOX-6 protein levels (a transcription factor with tumor suppressing properties) were also reduced. The observed dysregulated expression levels highlight the importance of ALDOA, MALAT-1, mir-122, mir-1271, and SOX-6, which remain less studied than the known and well-studied HIF1 pathways of VEGF, TGF-α, and EPO. Furthermore, inhibition of the up-regulated ALDOA, mir-122, and MALAT-1 could be of therapeutic interest for selected ccRCC patients.