Regulation of the small GTPase Ran by miR-802 modulates proliferation and metastasis in colorectal cancer cells
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Published:2020-03-25
Issue:11
Volume:122
Page:1695-1706
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ISSN:0007-0920
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Container-title:British Journal of Cancer
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language:en
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Short-container-title:Br J Cancer
Author:
Wang Xin, Li Danxiu, Sun Lina, Shen Gaofei, Liu Hao, Guo Hao, Ge Minghui, Liang Junrong, Chen Ping, Zhou Jinchi, Cao Tianyu, Wang Qi, Gao Xiaoliang, Tong Mingfu, Hu Sijun, Nie Yongzhan, Fan Daiming, wang xin, Zhao XiaodiORCID, Lu Yuanyuan
Abstract
Abstract
Background
The small GTPase Ran is upregulated in multiple cancers and fundamental for cancer cell survival and progression, but its significance and molecular mechanisms in colorectal cancer (CRC) remain elusive.
Methods
Ran expression was detected in CRC cell lines and tumour tissues. In vitro and in vivo functional assays were performed to examine the effects of Ran on cell proliferation and metastasis. The pathways and effectors regulated by Ran were explored by an unbiased screening. Bioinformatics prediction and experimental validation were used to identify the miRNA regulator for Ran.
Results
Ran expression was frequently increased in metastatic CRC cells and tissues, especially in metastatic tissues. The upregulation of Ran correlated with poor CRC patient prognosis. Ran silencing reduced proliferation and metastasis of CRC cells both in vitro and in vivo. Ran regulated the expression of EGFR and activation of ERK and AKT signalling pathways. miR-802 was identified as an upstream regulator of Ran and miR-802 overexpression resulted in antiproliferative and antimetastatic activities.
Conclusion
Our study demonstrates the oncogenic roles and underlying mechanisms of Ran in CRC and the novel miR-802/Ran/EGFR regulatory axis may provide potential biomarkers for the treatment of CRC.
Funder
National Natural Science Foundation of China National Key R&D Program of China Young Elite Scientists Sponsorship Program by cs National Science Fund for Excellent Young Scholars
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology
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