title: MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1.
abstract: MicroRNAs (miRNAs) that exert function by posttranscriptional suppression have recently brought insight in our understanding of the role of non-protein-coding RNAs in carcinogenesis and metastasis. In this study, we described the function and molecular mechanism of miR-139-5p in colorectal cancer (CRC) and its potential clinical application in CRC. We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues (NCTs), and decreased miR-139-5p was associated with poor prognosis. Functional analyses demonstrated that ectopic expression of miR-139-5p suppressed CRC cell migration and invasion in vitro and metastasis in vivo. Mechanistic investigations revealed that miR-139-5p suppress CRC cell invasion and metastasis by targeting AMFR and NOTCH1. Knockdown of the two genes phenocopied the inhibitory effect of miR-139-5p on CRC metastasis. Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression. Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients. Together, our data indicate that miR-139-5p is a potential tumor suppressor and prognostic factor for CRC, and targeting miR-139-5p may repress the metastasis of CRC and improve survival.
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, 214062, China.
authors.forename: Mingxu
authors.initials: M
authors.lastname: Song
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yin
authors.forename: Jiwei
authors.initials: J
authors.lastname: Zhang
authors.forename: Binbin
authors.initials: B
authors.lastname: Zhang
authors.forename: Zehua
authors.initials: Z
authors.lastname: Bian
authors.forename: Chao
authors.initials: C
authors.lastname: Quan
authors.forename: Leyuan
authors.initials: L
authors.lastname: Zhou
authors.forename: Yaling
authors.initials: Y
authors.lastname: Hu
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Wang
authors.forename: Shujuan
authors.initials: S
authors.lastname: Ni
authors.forename: Bojian
authors.initials: B
authors.lastname: Fei
authors.forename: Weili
authors.initials: W
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Du
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D060285:Receptors, Autocrine Motility Factor / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: C555098:MIRN139 microRNA, human; D035683:MicroRNAs; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; C555000:AMFR protein, human; D060285:Receptors, Autocrine Motility Factor