title: MicroRNA-143 targets MACC1 to inhibit cell invasion and migration in colorectal cancer.
abstract: BACKGROUND
  MicroRNAs (miRNAs) have been suggested to play a vital role in tumor initiation and progression by negatively regulating oncogenes and tumor suppressors. Quite recently, studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on anti-metastasis strategy. Metastasis-associated in colon cancer-1 (MACC1) has been newly identified to express highly in colorectal cancer (CRC) and promote tumor metastasis through transactivating metastasis-inducing HGF/MET signaling pathway. In this study, we investigated whether miRNA 143 is involved in the regulation of MACC1 and thus plays a functional role in CRC.
  
  
  RESULTS
  Using both in silico prediction and western blot assay, we found the previously reported tumor suppressive miR-143 targeted MACC1 in CRC. The direct interaction between them was confirmed by 3' UTR luciferase reporter gene. In concordance with the inhibitory effects induced by siRNA mediated knockdown of MACC1, restoration of miR-143 by mimics in SW620 cells significantly attenuated cell growth, migration and invasion. It is notable that combined treatment of miR-143 mimics and MACC1 siRNA induced synergistic inhibitory effects compared to either miR-143 mimics or MACC1 siRNA treatment alone. Conversely, reduction of miR-143 by inhibitors in SW480 cells apparently stimulated these phenotypes. Furthermore, we observed that miR-143 level was inversely correlated with MACC1 mRNA expression in CRC tissues.
  
  
  CONCLUSIONS
  Our findings newly described miR-143/MACC1 link and provided a potential mechanism for MACC1 dysregulation and contribution to CRC cell invasion. It may help to estimate the therapeutic utility of miR-143 in CRC.
authors.affiliation: Guangdong Provincial key laboratory of Gastroenterology, Department of Gastroenterology, Nangfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou, Guangdong Province 510515, P,R, China. drjiang@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.forename: Xinying
authors.initials: X
authors.lastname: Wang
authors.forename: Qunying
authors.initials: Q
authors.lastname: Ma
authors.forename: Fengli
authors.initials: F
authors.lastname: Ma
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D066298:In Vitro Techniques; D035683:MicroRNAs / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C544162:MACC1 protein, human; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D015534:Trans-Activators; D014157:Transcription Factors