Oncotarget

Research Papers:

MiR-384 inhibits human colorectal cancer metastasis by targeting KRAS and CDC42

Yong-Xia Wang, Yan-Ru Chen, Shan-Shan Liu, Ya-Ping Ye, Hong-Li Jiao, Shu-Yang Wang, Zhi-Yuan Xiao, Wen-Ting Wei, Jun-Feng Qiu, Li Liang, Wen-Ting Liao _ and Yan-Qing Ding

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Oncotarget. 2016; 7:84826-84838. https://doi.org/10.18632/oncotarget.12704

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Abstract

Yong-Xia Wang1,2,3,4,*, Yan-Ru Chen1,2,3,*, Shan-Shan Liu1,2,3,*, Ya-Ping Ye1,2,3, Hong-Li Jiao1,2,3, Shu-Yang Wang1,2,3, Zhi-Yuan Xiao1,2,3, Wen-Ting Wei1,2,3, Jun-Feng Qiu1,2,3, 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

4Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China

*These authors have contributed equally to this work

Correspondence to:

Wen-Ting Liao: email: liaowt2002@gmail.com

Yan-Qing Ding: email: dyq@fimmu.com

Keywords: colorectal cancer, MiR-384, metastasis, KRAS, CDC42

Received: July 20, 2016     Accepted: October 03, 2016     Published: October 17, 2016

ABSTRACT

Colorectal cancer (CRC) is the third most common cancer worldwide. Metastatic progression is a primary factor contributing to lethality of CRC patients. However, the molecular mechanisms forming early local invasion and distant metastatic colonies are still unclear and the present therapeutic approaches for CRC are unsatisfactory. Therefore, novel therapies targeting metastatic invasion that could prevent tumor spreading and recurrence are urgently needed. Our study showed that the decrease of miR-384 was found in 83.0% (83/100) CRC patients. And low-leveled expression of miR-384 was closely correlated with the invasive depth, lymph node and distant metastasis of CRC. Overexpression of miR-384 could inhibit the invasive and migrating abilities of CRC cells in vitro and the metastatic potential in vivo. Luciferase assays showed that miR-384 repressed the expression of Kirsten Ras (KRAS) and Cell division cycle 42 (CDC42) by directly targeting their 3’-untranslated regions. There is functional and mechanistic relationship between miRNA-384 and KRAS, CDC42 in the invasion and metastasis of CRC. And our findings suggest that miR-384could be a potent therapeutic target for CRC. Restoration of miR-384 expression might provide novel therapeutic approach to the reduction of CRC metastasis.


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