microRNA-375 inhibits colorectal cancer cells proliferation by downregulating JAK2/STAT3 and MAP3K8/ERK signaling pathways
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Ran Wei1,2,*, Qin Yang1,*, Bing Han1,3, Yan Li1, Kun Yao1, Xiuyu Yang1, Zexi Chen1,3, Shanshan Yang1, Jiaqi Zhou1, Meizhang Li1, Haijing Yu1, Min Yu1, Qinghua Cui1,2
1School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China
2Key Laboratory for tumor molecular biology in Yunnan Province, Yunnan University, Kunming, Yunnan, 650091, P.R. China
3Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, 650201, PR. China
*These authors contributed equally to this work
Qinghua Cui, email: email@example.com
Keywords: microRNA-375, colorectal cancer, JAK2/STAT3 pathway, MAP3K8/ERK pathway, ATG7
Received: July 14, 2016 Accepted: January 23, 2017 Published: February 06, 2017
MicroRNA-375 is involved in many types of alimentary system cancers. Our previous studies showed that microRNA-375 was significantly down-regulated in carcinoma tissues compared with para-carcinoma tissues, which strongly indicates that microRNA-375 might suppress the occurrence and development of colorectal cancer. However, the mechanism underlying the microRNA-375 regulation in colorectal cancer remains unclear. In this study, we first sorted out jak2, map3k8 and atg7 as microRNA-375 targeted genes from multiple databases, and found that jak2, map3k8 and their downstream genes stat3 and erk were up-regulated in carcinoma tissues. Secondly, we over-expressed microRNA-375 in colorectal cancer cell lines (HCT116, Caco2 and HT29). Our results showed that in microRNA-375 over-expressing cells, JAK2/STAT3 and MAP3K8/ERK proteins were down-regulated, cell proliferation was inhibited, cell migration rate did not change. There was no significant difference on ATG7 expression between the control group and microRNA-375 over-expressing HT29/Caco2 cells, whereas microRNA-375 down-regulated ATG7 specifically in HCT116 cells. Finally, we demonstrated that expressing microRNA-375 suppressed tumor formation in nude mice. In conclusion, microRNA-375 might function as a tumor-repressive gene to inhibit cell proliferation, mainly through targeting both JAK2/STAT3 and MAP3K8/ERK signaling pathways in colorectal cancer. These findings suggest miR-375 as a promising diagnostic marker and a therapeutic drug for colorectal cancer.
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