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Grainyhead-like 2 regulates epithelial plasticity and stemness in oral cancer cells.

Abstract：

:Grainyhead-like 2 (GRHL2) is one of the three mammalian homologues of Drosophila Grainyhead involved in epithelial morphogenesis. We recently showed that GRHL2 also controls normal epithelial cell proliferation and differentiation. In this study, we investigated the role of GRHL2 in oral carcinogenesis and the underlying mechanism. GRHL2 expression was elevated in cells and tissues of oral squamous cell carcinomas (OSCCs) compared with normal counterparts. Knockdown of GRHL2 resulted in the loss of in vivo tumorigenicity, cancer stemness and epithelial phenotype of oral cancer cells. GRHL2 loss also inhibited oral cancer cell proliferation and colony formation. GRHL2 regulated the expression of miR-200 family and Octamer-binding transcription factor 4 (Oct-4) genes through direct promoter DNA binding. Overexpression of miR-200 genes in the oral cancer cells depleted of GRHL2 partially restored the epithelial phenotype, proliferative rate and cancer stemness, indicating that miR-200 genes in part mediate the functional effects of GRHL2. Taken together, this study demonstrates a novel connection between GRHL2 and miR-200, and supports protumorigenic effect of GRHL2 on OSCCs.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Chen W,Yi JK,Shimane T,Mehrazarin S,Lin YL,Shin KH,Kim RH,Park NH,Kang MK

doi

10.1093/carcin/bgw027

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

500-10

issue

5

eissn

0143-3334

issn

1460-2180

pii

bgw027

journal_volume

37

pub_type

杂志文章

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