title: MicroRNA-146a promote cell migration and invasion in human colorectal cancer via carboxypeptidase M/src-FAK pathway.
abstract: Colorectal cancer (CRC) is one of the most common cancers worldwide, and microRNAs play important roles in CRC progression. This study aimed to investigate the roles of miR-146a-5p in human CRC and their molecular mechanisms. First, we found that miR-146a-5p was significantly upregulated in CRC tissues and promoted the migration of CRC cells. Then, we identified carboxypeptidase M (CPM) as a direct target of miR-146a-5p, and found that it inhibited the migration and invasion of CRC cells. Our results also showed that CPM expression was positively correlated with overall survival and negatively correlated with recurrence, lymph node invasion, and N stage. Furthermore, we demonstrated that both miR-146a-5p and CPM regulated Src and FAK expression, while the Src-FAK signaling pathway is widely known to be associated with the migration and invasion of multiple tumor cells. This study is the first to demonstrate the functional and mechanistic relationship of the miR-146a-5p/CPM/Src-FAK axis and its effect on the migration and invasion of CRC cells. Thus, miR-146a-5p represents potential targets for CRC diagnosis and therapy.
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Di
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Qunyan
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhan
authors.affiliation: Department of The Affiliated Cancer Hospital, Xiang Ya School of Medicine, Central South University, Changsha, Hunan, 410013, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Le-Meng
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Hongchun
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Chuantao
authors.initials: C
authors.lastname: Tu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Yanting
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Shuncai
authors.initials: S
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015398:Signal Transduction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; C058479:carboxypeptidase M; D008666:Metalloendopeptidases
keywords: carboxypeptidase M; colorectal cancer; invasion; miR-146a-5p; migration