title: Down-regualtion of miR-106b induces epithelial-mesenchymal transition but suppresses metastatic colonization by targeting Prrx1 in colorectal cancer.
abstract: Accumulating evidence identified that epithelial-mesenchymal transition (EMT) is acquired during progression to metastatic, but whether it is an absolute requirement is still controversial. MiR-106b has been confirmed to promote cancer cell proliferation; however few studies are available on its functions in EMT and metastasis in colorectal cancer (CRC). In this study, we found that knocking down miR-106b induced EMT conferring migratory and invasive properties. MiR-106b knockdown induced cytoskeletal reorganization through staining intracellular F-actin. The expression of Rho GTPases (Rac1 and Cdc42) and Tiam1 was significantly enforced after miR-106b down-regulation. However, miR-106b knocking down could suppress metastatic colonization in vivo. Correspondingly, over expression of miR-106b obtained an opposite effect. We identified Prrx1 was a direct target of miR-106b through using target prediction algorithms and dual-Luciferase reporter assay. Moreover, Moreover, we also found TGF-β1 could down-regulate miR-106b, and simultaneously miR-106b also influences the expression of TGF-β1, establishing a negative feedback loop to regulate the expression of Prrx1 together. Taken together, these findings demonstrated that miR-106b knockdown could induce EMT which conferring cells migratory and invasive properties but could not accomplish distant metastatic colonization efficiently.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University Guangzhou 510515, Guangdong Province, China ; Department of Pathology, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong Province, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Jinan University Guangzhou 510630, Guangdong Province, China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong Province, China.
authors.forename: Shuimiao
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong Province, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Sun
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong Province, China.
authors.forename: Runze
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong Province, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University Guangzhou 510515, Guangdong Province, China ; Department of Pathology, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong Province, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Ding
mesh_terms: D015153:Blotting, Western; D002465:Cell Movement / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering; D014162:Transfection
chemical_list: D018398:Homeodomain Proteins; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; C082157:PRRX1 protein, human; D034741:RNA, Small Interfering
keywords: EMT; Prrx1; colorectal cancer; metastasis; miR-106b