Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer affecting many people worldwide. Although the 5-year survival rate is 65% in localized disease, after metastasis, the survival rate is <10%. Emerging evidence has shown that microRNAs (miRNAs) play a crucial regulatory role in the progression of ccRCC. Here, we show that miR-335, an anti-onco-miRNA, is downregulation in tumor tissue and inhibited ccRCC cell proliferation, invasion, and migration. Our studies further identify the H3K9me1/2 histone demethylase KDM3A as a new miR-335-regulated gene. We show that KDM3A is overexpressed in ccRCC, and its upregulation contributes to the carcinogenesis and metastasis of ccRCC. Moreover, with the overexpression of KDM3A, YAP1 was increased and identified as a direct downstream target of KDM3A. Enrichment of KDM3A demethylase on YAP1 promoter was confirmed by CHIP-qPCR and YAP1 was also found involved in the cell growth and metastasis inhibitory of miR-335. Together, our study establishes a new miR-335/KDM3A/YAP1 regulation axis, which provided new insight and potential targeting of the metastasized ccRCC.
Highlights
Renal cell cancer (RCC) is one of the most common malignancies worldwide
The effect of miR335 or KDM3A was reversed when simultaneously cotransfected with miR-335 mimics and KDM3A overexpression plasmids. These findings indicate that KDM3A is an important oncogene in Clear cell renal cell carcinoma (ccRCC), and promotes tumor growth and metastasis while functioning as the main executor of miR-335
Over 300 diseases have been correlated with miRNAs, including oncological diseases [21]. miRNAs may regulate all characteristics of tumors, including control of cell proliferation, apoptosis, angiogenesis, tissue invasion, and metastasis
Summary
Renal cell cancer (RCC) is one of the most common malignancies worldwide. Based on global cancer 2018 statistics, more than 400,000 patients were newly diagnosed, while more than 170,000 deaths were due to RCC each year [1]. Among all types of RCC, clear cell renal cell carcinoma (ccRCC, called KIRC) is the most common subtype that accounts for 65–70% of all renal cancers [1, 2]. The 5-year survival rate of localized ccRCC is 65%, once the tumor has metastasized, the 5-year survival rate is
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