Format

Send to

Choose Destination
Gastroenterology. 2010 Jan;138(1):231-40.e1-5. doi: 10.1053/j.gastro.2009.08.001. Epub 2009 Aug 15.

RNA-binding protein quaking, a critical regulator of colon epithelial differentiation and a suppressor of colon cancer.

Author information

1
The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi'an, China.

Abstract

BACKGROUND & AIMS:

Colon cancer is one of the best understood neoplasms from a genetic perspective, yet it remains the second most common cause of cancer-related death. Post-transcriptional regulation mediated by RNA-binding proteins or microRNAs coordinately targets multiple genes, holding promise involved in colon cancer initiation and development. Here we studied the role of RNA-binding protein quaking (QKI) in colon cancer.

METHODS:

We observed the expression pattern of QKI in normal colon and colon cancers through reverse-transcription polymerase chain reaction and Western blot. Bisulfite sequencing and methylation-specific PCR were applied for QKI promoter methylation analysis. We used enterocyte differentiation markers and soft agar assay to test the role of QKI in colon differentiation and colon cancer development. 3' Untranslated region (UTR) reporter assay and RNA-immunoprecipitation were used to confirm the interaction between QKI and beta-catenin or p27.

RESULTS:

QKI is significantly down-regulated and even absent in some colon cancers, which is at least partially because of the promoter hypermethylation. Forced expression of QKI in the colon cancer cells increased the expression of enterocyte differentiation marker intestinal alkaline phosphatase and lactase, together with the enhancement of p27Kip1 protein level, and membrane localized beta-catenin. Finally, QKI overexpression reduced the proliferation and tumorigenesis ability.

CONCLUSIONS:

Our study establishes that QKI functions as a principal regulator in the differentiation of colon epithelium and a suppressor of carcinogenesis through coordinately targeting multiple genes associated with cell growth and differentiation, whose deregulation by methylation is involved in colon cancer onset and progress.

PMID:
19686745
PMCID:
PMC2847771
DOI:
10.1053/j.gastro.2009.08.001
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center