title: MicroRNA-544a Regulates Migration and Invasion in Colorectal Cancer Cells via Regulation of Homeobox A10.
abstract: MicroRNAs (miRNAs) are a group of small RNA molecules that post-transcriptionally regulate gene expression. Aberrant expression of miRNAs has been associated with tumorigenesis in various cancers. miR-544a is an understudied miRNA that has recently been implicated in regulating invasion in lung cancer. However, its role in regulating invasion and the underlying mechanism have not been investigated in colorectal cancer (CRC) cells.
  
  
  
  Microarray analysis was performed in metastatic colorectal tumor samples and their matched normal tissues to identify differentially expressed miRNAs. Quantitative real-time PCR was used to detect miR-544a levels in tumor samples and CRC cell lines with varying metastatic properties. miR-544a mimic or inhibitor was transfected into SW480 and HCT116 cells, respectively, followed by wound healing and invasion assays. Western Blot and luciferase assay were performed to investigate the direct target of miR-544a. Xenograft mouse models was used to examine in vivo function of miR-544a.
  
  
  
  Our data showed that expression of miR-544a was significantly up-regulated in metastatic tumor samples and CRC cell lines. Inhibition of miR-544a reduced migration and invasion in HCT116 cells. Homeobox A10 (HOXA10) was the direct target of miR-544a which was required for the function of miR-544a in regulating invasiveness. miR-544a inhibitor and/or HOXA10 overexpression reduced lung metastases in HCT116 xenografts.
  
  
  
  Our study demonstrates that miR-544a regulates invasive and metastatic properties of CRC cells by modulating HOXA10 expression level both in vitro and in vivo. miR-544a may represent a new therapeutic target for the intervention of metastatic colorectal cancer.
authors.affiliation: Department of Colorectal Anal Surgery, The Central Hospital of Zaozhuang Mining Group of Shandong, Qilianshan Road, High-tech Zone, Zaozhuang, 277800, Shandong, China. shangfengsun@sina.com.
authors.forename: Shangfeng
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Colorectal Anal Surgery, The Central Hospital of Zaozhuang Mining Group of Shandong, Qilianshan Road, High-tech Zone, Zaozhuang, 277800, Shandong, China.
authors.forename: Changying
authors.initials: C
authors.lastname: Su
authors.affiliation: Department of Colorectal Anal Surgery, The Central Hospital of Zaozhuang Mining Group of Shandong, Qilianshan Road, High-tech Zone, Zaozhuang, 277800, Shandong, China.
authors.forename: Yunxiao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Colorectal Anal Surgery, The Central Hospital of Zaozhuang Mining Group of Shandong, Qilianshan Road, High-tech Zone, Zaozhuang, 277800, Shandong, China. haiyanlii@sina.com.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Information Technology, Jining Medical University, Hehua Road, Jining, 272067, Shandong, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical University, Guhuai Road, Jining, 272029, Shandong, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Xu
authors.affiliation: Central Laboratory, Second Hospital of Shandong University, Jinan, 250014, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Second Hospital of Shandong University, Jinan, 250014, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Lv
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018938:Caco-2 Cells; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D045325:HCT116 Cells; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C582640:MIRN544 microRNA, human; D035683:MicroRNAs; C069634:HOXA10 protein, human; C092119:Hoxa10 protein, mouse
keywords: Colorectal cancer; HOXA10; Invasion; Migration; miR-544a