Epigenetic regulation of human DCLK-1 gene during colon-carcinogenesis: clinical and mechanistic implications

摘要: Colorectal carcinogenesis is a multi-step process. While ~25% of colorectal cancers (CRCs) arise in patients with family history (genetic predisposition), ~75% CRCs are due to age-associated accumulation epigenetic alterations which can result the suppression key tumor suppressor genes leading mutations and activation oncogenic pathways. Sporadic colon-carcinogenesis facilitated by many molecular pathways genomic instability include chromosomal (CIN), micro-satellite (MSI) CpG island methylator phenotype (CIMP), towards loss homeostasis onset neoplastic transformation. The unopposed Wnt/β-catenin pathways, either APC function or up-regulation related stimulatory results hyperproliferation colonic crypts, considered single most important risk factor for colon carcinogenesis. Hypermethylation islands within promoters specific potentially inactivate DNA repair and/or critical genes. Recently, methylation 5’ promoter human (h) DCLK1 gene was reported epithelial cancers, including (CRCs), resulting expression canonical long isoform (DCLK1-L) hCRCs. Instead, shorter (DCLK1-S) discovered be expressed hCRCs, from an alternate β DCLKL1 -gene; clinical biological implications these novel findings, relation recent publications discussed.