title: miR-143 decreases prostate cancer cells proliferation and migration and enhances their sensitivity to docetaxel through suppression of KRAS.
abstract: MicroRNAs have been implicated in regulating diverse cellular pathways. Emerging evidence indicates that miR-143 plays causal roles in cancer tumorigenesis as a tumor suppress gene; however, its role in prostate cancer tumorigenesis remains largely unknown. The aims of this study were to verify the effect of miR-143 on proliferation and migration abilities of prostate cancer cells. The expression level of miR-143 and its target gene KRAS were measured by realtime PCR and western blotting, respectively. Effects of miR-143 in cell proliferation, migration and chemosensitivity were evaluated by MTT assay, FACS cell cycle analysis, colony formation assay, and transwell migratory assay. Our results revealed an inverse correlation of expression between miR-143 and KRAS protein in prostate cancer samples (Pearson's correlation scatter plots: R = -0.707, P < 0.05). Moreover, over-expression of miR-143 in prostate cancer cells suppressed their proliferation and migration and increased their sensitivity to docetaxel by targeting EGFR/RAS/MAPK pathway. These findings suggest that miR-143 plays an important role in prostate cancer proliferation, migration and chemosensitivity by suppressing KRAS and subsequent inactivation of MAPK pathway, which provides a potential development of a new approach for the treatment of prostate cancer.
authors.affiliation: Department of Urology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Niu
authors.forename: Xiangxiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Tao
authors.forename: Deyao
authors.initials: D
authors.lastname: Wu
authors.forename: Zidun
authors.initials: Z
authors.lastname: Wang
authors.forename: Pengchao
authors.initials: P
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hongfei
authors.initials: H
authors.lastname: Wu
authors.forename: Ninghan
authors.initials: N
authors.lastname: Feng
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Wang
authors.forename: Lixin
authors.initials: L
authors.lastname: Hua
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D000077143:Docetaxel; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D019940:Genes, bcl-1; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D043823:Taxoids; D000077143:Docetaxel; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins