Oncotarget

Research Papers:

miR-450b-5p induced by oncogenic KRAS is required for colorectal cancer progression

Ya-Ping Ye, Ping Wu, Chun-cai Gu, Dan-ling Deng, Hong-Li Jiao, Ting-Ting Li, Shu-Yang Wang, Yong-Xia Wang, Zhi-Yuan Xiao, Wen-ting Wei, Yan-Ru Chen, Jun-Feng Qiu, Run-Wei Yang, Jie Lin, Li Liang, Wen-Ting Liao _ and Yan-Qing Ding

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Oncotarget. 2016; 7:61312-61324. https://doi.org/10.18632/oncotarget.11016

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Abstract

Ya-Ping Ye1,2,3,*, Ping Wu1,2,3,*, Chun-cai Gu1,2,3,*, Dan-ling Deng1,2,3, Hong-Li Jiao1,2,3, Ting-Ting Li1,2,3, Shu-Yang Wang1,2,3, Yong-Xia Wang1,2,3, Zhi-Yuan Xiao1,2,3, Wen-ting Wei1,2,3, Yan-Ru Chen1,2,3, Jun-Feng Qiu1,2,3, Run-Wei Yang1,2,3, Jie Lin1,2,3, Li Liang1,2,3, Wen-Ting Liao1,2,3, Yan-Qing Ding1,2,3

1Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

2Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China

3Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China

*These authors have contributed equally to this work

Correspondence to:

Wen-Ting Liao, email: [email protected]

Yan-Qing Ding, email: [email protected]

Keywords: miR-450b-5p, Wnt/β-Catenin pathway, colorectal cancer, progression, KRAS

Received: May 13, 2016    Accepted: July 14, 2016    Published: August 2, 2016

ABSTRACT

The development and progression of CRC are regarded as a complicated network and progressive event including genetic and/or epigenetic alterations. Recent researches revealed that MicroRNAs are biomarkers and regulators of CRC progression. Analyses of published microarray datasets revealed that miR-450b-5p was highly up-regulated in CRC tissues. In addition, high expression of miR-450b-5p was significantly associated with KRAS mutation. However, the role of miR-450b-5p in the progression of CRC remains unknown. Here, we sought to validate the expression of miR-450b-5p in CRC tissues and investigate the role and underlying mechanism of miR-450b-5p in the progression of CRC. The results revealed that miR-450b-5p was up-regulated in CRC tissues, high expression level of miR-450b-5p was positively associated with poor differentiation, advanced TNM classification and poor prognosis. Moreover, miR-450b-5p was especially high in KRAS-mutated cell lines and could be up-regulated by KRAS/AP-1 signaling. Functional validation revealed that overexpression of miR-450b-5p promoted cell proliferation and tumor growth while inhibited apoptosis of CRC cells. Furthermore, we demonstrated that miR-450b-5p directly bound the 3’-UTRs of SFRP2 and SIAH1, and activated Wnt/β-Catenin signaling. In conclusion, miR-450b-5p induced by oncogenic KRAS is required for colorectal cancer progression. Collectively, our work helped to understand the precise role of miR-450b-5p in the progression of CRC, and might promote the development of new therapeutic strategies against CRC.


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