title: MicroRNA-224 suppresses colorectal cancer cell migration by targeting Cdc42.
abstract: The metastatic spread of tumor cells is the major risk factor affecting the clinical prognosis of colorectal cancer (CRC) patients. The metastatic phenotype can be modulated by dysregulating the synthesis of different structural and functional proteins of tumor cells. Micro(mi)RNAs are noncoding RNAs that recognize their cognate messenger (m)RNA targets by sequence-specific interactions with the 3' untranslated region and are involved in the multistep process of CRC development. The objective of this study was to investigate the expression and biological roles of miR-224 in CRC. The miR-224 expression level was assessed by a quantitative real-time PCR in 79 CRC and 18 nontumor tissues. Expression levels of miR-224 in CRC tissues were significantly lower than those in nontumor tissues. Its expression level was associated with the mutation status of the APC gene. Ectopic expression of miR-224 suppressed the migratory ability of CRC cell line, but cell proliferation was less affected. Increased miR-224 diminished Cdc42 and SMAD4 expressions at both the protein and mRNA levels and inhibited the formation of actin filaments. Overall, this study indicated a role of miR-224 in negatively regulating CRC cell migration. The expression level of miR-224 may be a useful predictive biomarker for CRC progression.
authors.affiliation: Institute of Medicine, Chung-Shan Medical University, Taichung 402, Taiwan ; Division of Colorectal Surgery, Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan.
authors.forename: Tao-Wei
authors.identifier: 0000-0001-6847-4008
authors.initials: TW
authors.lastname: Ke
authors.affiliation: Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei 116, Taiwan.
authors.forename: Han-Lin
authors.initials: HL
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Wu
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan.
authors.forename: William Tzu-Liang
authors.initials: WT
authors.lastname: Chen
authors.affiliation: PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Cheng
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan ; Center for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan ; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chao-Wen
authors.identifier: 0000-0002-0466-6630
authors.initials: CW
authors.lastname: Cheng
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D034622:RNA Interference; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D000199:Actins; C546140:MIRN224 microRNA, human; D035683:MicroRNAs; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D020764:cdc42 GTP-Binding Protein