title: miR-15a-3p and miR-16-1-3p Negatively Regulate Twist1 to Repress Gastric Cancer Cell Invasion and Metastasis.
abstract: MicroRNAs are a novel class of gene regulators that function as oncogenes or tumor suppressors. In our current study, we investigated the role of miR-15a-3p and miR-16-1-3p in the regulation ofTwist1expression and EMT process. Our bioinformatics analysis suggested that on the 3' UTR ofTwist1, there are two conserved miRNA recognition sites for miR-15a-3p and miR-16-1-3p respectively. Interestingly, overexpression of miR-15a-3p and miR-16-1-3p significantly suppressed the activity of luciferase reporter containingTwist1-3' UTR, reduced mRNA and protein level of EMT related genes such as TWIST1, N-cadherin, α-SMA and Fibronectin, and repressed MMP9 and MMP2 activity, as well as cell migration and invasion. Conversely, inhibition of miR-15a-3p and miR-16-1-3p significantly increased TWIST1, N-cadherin, α-SMA and Fibronectin protein expression. In addition,Twist1co-transfection significantly ameliorated the loss of cell migration and invasion. Moreover, overexpression of miR-15a-3p and miR-16-1-3p dramatically suppressed the ability of BGC823 cells to form coloniesin vitroand develop tumorsin vivoin nude mice. Finally, qPCR and Western blot analysis showed that miR-15a-3p and miR-16-1-3p were significantly reduced in clinical gastric cancer tissue, whereasTwist1mRNA and protein were significantly up-regulated, suggesting that this aberrant down-regulation of miR-15a-3p and miR-16-1-3p might be associated with the abnormal regulation of Twist1 and the EMT process in gastric cancer development. Our results help to elucidate a novel and important mechanism for the regulation ofTwist1in the development of cancer.
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital affiliated to Xiamen University, Xiamen, China 361004.; Institute of Gastrointestinal Oncology, Medical college of Xiamen University, Xiang'an, Xiamen, China 361102.; Xiehe Clinical Medical College, Fujian Medical University, Fuzhou, China 350001.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital affiliated to Xiamen University, Xiamen, China 361004.; Institute of Gastrointestinal Oncology, Medical college of Xiamen University, Xiang'an, Xiamen, China 361102.; Xiehe Clinical Medical College, Fujian Medical University, Fuzhou, China 350001.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Hou
authors.affiliation: State Key Laboratory Breeding Base of Marine Genetic Resources, Third Institute of Oceanography, State Oceanic Administration, 184 University Road, Xiamen, China 361005.
authors.forename: Zengpeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: College of Arts and Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514.
authors.forename: Zihan
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Basic Medical Sciences of Medical College, Xiamen University, Xiang'an, Xiamen, China 361102.
authors.forename: Jie
authors.initials: J
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Cellular Stress Biology and Department of Biomedical Sciences, School of Life Sciences, Xiamen University, Xiang'an, Xiamen, China 361102.
authors.forename: Dan
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Basic Medical Sciences of Medical College, Xiamen University, Xiang'an, Xiamen, China 361102.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Cellular Stress Biology and Department of Biomedical Sciences, School of Life Sciences, Xiamen University, Xiang'an, Xiamen, China 361102.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cellular Stress Biology and Department of Biomedical Sciences, School of Life Sciences, Xiamen University, Xiang'an, Xiamen, China 361102.
authors.forename: James Y
authors.initials: JY
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital affiliated to Xiamen University, Xiamen, China 361004.; Institute of Gastrointestinal Oncology, Medical college of Xiamen University, Xiang'an, Xiamen, China 361102.; Xiehe Clinical Medical College, Fujian Medical University, Fuzhou, China 350001.
authors.forename: Jian-Chun
authors.initials: JC
authors.lastname: Cai
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; C544301:Mirn15a microRNA, mouse; C522604:Mirn16 microRNA, mouse; D051879:Twist-Related Protein 1
keywords: Gastric cancer; Twist1; cell invasion and metastasis.; miR-15a-3p; miR-16-1-3p