title: MicroRNA-126 functions as a tumor suppressor in colorectal cancer cells by targeting CXCR4 via the AKT and ERK1/2 signaling pathways.
abstract: Recent evidence shows that altered microRNA-126 (miR-126) expression is implicated in the progression of colorectal cancer (CRC). However, the precise roles and mechanisms of miR-126 in CRC remain unclear. The aim of this study was to investigate the roles of miR-126 in CRC cells and to elucidate miR-126-mediated mechanisms in CRC cells. First, miR-126 expression was analyzed using qRT-PCR in 4 human CRC cell lines (SW480, SW620, HT-29 and HCT-116). Furthermore, the biological properties of miR-126 in CRC cells in vitro were examined by applying Cell Counting Kit 8, cell cycle, cell apoptosis and transwell assays. The mechanisms and pathways of miR-126-mediated in CRC cells were detected by using qRT-PCR, western blotting and luciferase reporter assay. We found that miR-126 overexpression inhibited cell proliferation, migration and invasion, and induced cell arrest in the G0/G1 phase of CRC cells, suggesting that miR-126 functions as a tumor suppressor in CRC cells. Furthermore, we identified the CXC chemokine receptor 4 (CXCR4) as a target of miR-126, and showed that it was negatively regulated by miR-126. We demonstrated that miR-126-mediated tumor suppression might be partly dependent on AKT and ERK1/2 signaling pathways. In conclusion, our data revealed that miR-126 functions as a tumor suppressor in CRC cells by regulating CXCR4 expression via the AKT and ERK1/2 signaling pathways and might be a novel target for therapeutic strategies in CRC.
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiao
authors.initials: X
authors.lastname: Feng
authors.forename: Ping
authors.initials: P
authors.lastname: An
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Quan
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Shicai
authors.initials: S
authors.lastname: Ye
authors.forename: Caiyuan
authors.initials: C
authors.lastname: Yu
authors.forename: Yanting
authors.initials: Y
authors.lastname: He
authors.forename: Hesheng
authors.initials: H
authors.lastname: Luo
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D051058:Oncogene Protein v-akt / Q000235:genetics*; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism
chemical_list: C527276:CXCR4 protein, human; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D019718:Receptors, CXCR4; D051058:Oncogene Protein v-akt