Epigenetic Repression of miR-217 Contributes to Tobacco-Induced Esophageal Carcinogenesis

Wednesday, November 06, 2013 — Poster Session I
4:00 p.m. – 6:00 p.m.	FAES Academic Center (Upper-Level Terrace)	NCI	CANCER-19

Authors

S Xi
S Inchauste
H Guo
J Shan
Z Xiao
M Zhang
JA Hong
SO Oyetunji
DG Beer
DS Schrump

Abstract

Limited information is available regarding mechanisms by which these noncoding RNAs contribute to initiation and progression of tobacco-induced esophageal cancers up to date. Here we examine miRNA expression profiles in esophageal epithelial cells (Het-1A), as well as EsC-1 and EsC-2 esophageal cancer cells when exposed to cigarette smoke condensate (CSC). CSC significantly decreased miR-217 expression in esophageal cancer cells and Het-1A cells. Endogenous miR-217 expression levels in cultured esophageal cancer cells were significantly lower than those observed in Het-1A cells and similar phenomenon was also found in resected esophageal cancers relative to adjacent normal esophageal tissues. Constitutive over-expression of miR-217 inhibited expression, whereas depletion of endogenous miR-217 enhanced expression of KLK7 (potential oncogene target of miR-217) in Het-1A, EsC1 and EsC2 cells. Ago-CLIP experiments confirmed direct interaction of miR-217 with KLK7 transcripts. MeDIP and ChIP experiments demonstrated that CSC increased DNA methylation and decreased H3K4me3 levels in those cells. Deoxyazacytidine induced miR-217 expression in EsC1 and EsC2 cells but not Het-1A cells, and markedly attenuated CSC-mediated miR-217 repression in these cells. Over-expression of miR-217 significantly decreased proliferation and invasion of esophageal cancer cells. Collectively, these data demonstrate that epigenetic repression of miR-217 contributes to the pathogenesis of esophageal carcinomas.