title: miR-320a suppresses colorectal cancer progression by targeting Rac1.
abstract: MicroRNAs (miRNAs) have emerged as critical epigenetic regulators involved in cancer progression. miR-320a has been identified to be a novel tumour suppressive miRNA in colorectal cancer (CRC). However, the detailed molecular mechanisms are not fully understood. Here, we reported that miR-320a inversely associated with CRC aggressiveness in both cell lines and clinical specimens. Functional studies demonstrated that miR-320a significantly decreased the capability of cell migration/invasion and induced G0/G1 growth arrest in vitro and in vivo. Furthermore, Rac1 was identified as one of the direct downstream targets of miR-320a and miR-320a specifically binds to the conserved 8-mer at position 1140-1147 of Rac1 3'-untranslated region to regulate Rac1 protein expression. Over-expression of miR-320a in SW620 cells inhibited Rac1 expression, whereas reduction of miR-320a by anti-miR-320a in SW480 cells enhanced Rac1 expression. Re-expression of Rac1 in the SW620/miR-320a cells restored the cell migration/invasion inhibited by miR-320a, whereas knockdown of Rac1 in the SW480/anti-miR-320a cells repressed these cellular functions elevated by anti-miR-320a. Conclusively, our results demonstrate that miR-320a functions as a tumour-suppressive miRNA through targeting Rac1 in CRC.
authors.affiliation: Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, People's Republic of China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Zhao
authors.forename: Taotao
authors.initials: T
authors.lastname: Dong
authors.forename: Houmin
authors.initials: H
authors.lastname: Zhou
authors.forename: Linlin
authors.initials: L
authors.lastname: Wang
authors.forename: Ao
authors.initials: A
authors.lastname: Huang
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Quan
authors.forename: Runsen
authors.initials: R
authors.lastname: Jin
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Daohai
authors.initials: D
authors.lastname: Zhang
authors.forename: Minhua
authors.initials: M
authors.lastname: Zheng
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D017931:DNA Primers; D018450:Disease Progression; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D060888:Real-Time Polymerase Chain Reaction; D020830:rac1 GTP-Binding Protein / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D017931:DNA Primers; C572916:MIRN320 microRNA, human; D035683:MicroRNAs; C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein