title: microRNA-375 inhibits colorectal cancer cells proliferation by downregulating JAK2/STAT3 and MAP3K8/ERK signaling pathways.
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.
authors.affiliation: School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China.|Key Laboratory for Tumor Molecular Biology in Yunnan Province, Yunnan University, Kunming, Yunnan, 650091, P.R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Wei
authors.affiliation: School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China.|Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, 650201, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yao
authors.affiliation: School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China.
authors.forename: Xiuyu
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China.|Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, 650201, P.R. China.
authors.forename: Zexi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yang
authors.affiliation: School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Zhou
authors.affiliation: School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China.
authors.forename: Meizhang
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China.
authors.forename: Haijing
authors.initials: H
authors.lastname: Yu
authors.affiliation: School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China.|Key Laboratory for Tumor Molecular Biology in Yunnan Province, Yunnan University, Kunming, Yunnan, 650091, P.R. China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Cui
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000502:physiology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D064593:Heterografts; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human
keywords: ATG7; JAK2/STAT3 pathway; MAP3K8/ERK pathway; colorectal cancer; microRNA-375