Work

microRNA-375 inhibits colorectal cancer cells proliferation by downregulating JAK2/STAT3 and MAP3K8/ERK signaling pathways

Year: 2017

Type: article

Abstract: // Ran Wei 1, 2, * , Qin Yang 1, * , Bing Han 1, 3 , Yan Li 1 , Kun Yao 1 , Xiuyu Yang 1 , Zexi Chen 1, 3 , Shanshan Yang 1 , Jiaqi Zhou 1 , Meizhang Li 1 , Haijing Yu 1 , Min Yu 1 , Qinghua Cui 1, 2 1 School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China 2 Key Laboratory for tumor molecular biology in Yunnan Province, Yunnan University, Kunming, Yunnan, 650091, P.R. China 3 Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, 650201, PR. China * These authors contributed equally to this work Correspondence to: Qinghua Cui, email: [email protected] Keywords: microRNA-375, colorectal cancer, JAK2/STAT3 pathway, MAP3K8/ERK pathway, ATG7 Received: July 14, 2016 Accepted: January 23, 2017 Published: February 06, 2017 ABSTRACT 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.

Source: Oncotarget

DOI: 10.18632/oncotarget.15114