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

Ectopic expression DNMT1
DOI: 10.1038/cddis.2017.323 Publication Date: 2017-07-27T12:42:59Z
ABSTRACT
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.
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