DNMT1-maintained hypermethylation of Krüppel-like factor 5 involves in the progression of clear cell renal cell carcinoma

• DOI: 10.1038/cddis.2017.323
• Publication Date: 2017-07-27T12:42:59Z
• Authors: Rong-Jie Fu; Wei He; Xiao-Bo Wang; Lei Li; Huan-Bin Zhao; Xiao-Ye Liu; Zhi Pang; Guo-Qiang Chen; Lei Huang; Ke-Wen Zhao
• Keywords: Ectopic expression; DNMT1

Clear cell renal carcinoma (ccRCC) is the major subtype of (RCC) that resistant to conventional radiation and chemotherapy. It a challenge explore effective therapeutic targets drugs for this kind cancer. Transcription factor Krüppel-like 5 (KLF5) exerts diverse functions in various tumor types. By analyzing cohorts Cancer Genome Atlas (TCGA) data sets, we find KLF5 expression suppressed ccRCC patients higher level associated with better prognostic outcome. Our further investigations demonstrate genomic loci are hypermethylated at proximal exon 4 suppression DNA methyltransferase 1 (DNMT1) by ShRNAs or methylation inhibitor 5-Aza-CdR can recover expression. Meanwhile, there negative correlation between expressions DNMT1 tissues. Ectopic inhibits proliferation migration/invasion vitro decreases xenograft growth metastasis vivo. Moreover, 5-Aza-CdR, chemotherapy drug as DNMTs' induce expression, suppresses growth, while knockdown abolishes 5-Aza-CdR-induced inhibition. Collectively, our suppressor highlight potential release modality treatment ccRCC.