Oncotarget

Priority Research Papers:

Dicer suppresses cytoskeleton remodeling and tumorigenesis of colorectal epithelium by miR-324-5p mediated suppression of HMGXB3 and WASF-2

Li Na Sun _, Cheng Xing, Zheng Zhi, Yao Liu, Liang-Yan Chen, Tong Shen, Qun Zhou, Yu Hong Liu, Wen Juan Gan, Jing-Ru Wang, Yong Xu and Jian Ming Li

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:55776-55789. https://doi.org/10.18632/oncotarget.18218

Metrics: PDF 2390 views  |   HTML 3503 views  |   ?  


Abstract

Li Na Sun1,*, Cheng Xing1,*, Zheng Zhi1, Yao Liu1, Liang-Yan Chen1, Tong Shen1, Qun Zhou1, Yu Hong Liu2, Wen Juan Gan1, Jing-Ru Wang1, Yong Xu3 and Jian Ming Li1

1 Department of Pathology and Pathophysiology, Soochow University Medical School, Suzhou, People’s Republic of China

2 Department of Pathology, Baoan Hospital, Southern Medical University, Shenzhen, People’s Republic of China

3 Department of Pathophysiology, Nanjing Medical University, Nanjing, People’s Republic of China

* These authors have contributed equally to this work

Correspondence to:

Jian Ming Li, email:

Keywords: dicer, miRNA, cytoskeleton remodeling, tumorgenesis, colorectal cancer

Received: January 09, 2017 Accepted: May 12, 2017 Published: May 25, 2017

Abstract

Emerging evidence indicates that microRNAs, a class of small and well-conserved noncoding RNAs, participate in many physiological and pathological processes. RNase III endonuclease DICER is one of the key enzymes for microRNA biogenesis. Here, we found that DICER was downregulated in tumor samples of colorectal cancer (CRC) patients at both mRNA and protein levels. Importantly, intestinal epithelial cell (IEC)-specific deletion of Dicer mice got more tumors after azoxymethane and dextran sulfate sodium (DSS) administration. Interestingly, IEC-specific deletion of Dicer led to severe chronic inflammation and epithelium layer remodeling in mice with or without DSS administration. Microarray analysis of 3 paired Dicer deletion CRC cell lines showed that miR-324-5p was one of the most significantly decreased miRNAs. In the intestinal epithelium of IEC-specific deletion of Dicer mice, miR-324-5p was also found to be markedly reduced. Mechanistically, miR-324-5p directly bound to the 3’untranslated regions (3’UTRs) of HMG-box containing 3 (HMGXB3) and WAS protein family member 2 (WASF-2), two key proteins participated in cell motility and cytoskeleton remodeling, to suppress their expressions. Intraperitoneal injection of miR-324-5p AgomiR (an agonist of miR-324-5p) curtailed chronic inflammation and cytoskeleton remodeling of colorectal epithelium and restored intestinal barrier function in IEC-specific deletion of Dicer mice induced by DSS. Therefore, our study reveals a key role of a DICER/miR-324-5p/HMGXB3/WASF-2 axis in tumorigenesis of CRC by regulation of cytoskeleton remodeling and maintaining integrity of intestinal barriers.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 18218