title: miR-133a represses tumour growth and metastasis in colorectal cancer by targeting LIM and SH3 protein 1 and inhibiting the MAPK pathway.
abstract: In recent studies of microRNA expression, miR-133a deregulation was identified in colorectal carcinoma (CRC). However, the mechanisms underlying the pathogenesis and progression of CRC are poorly understood. We found that miR-133a expression was usually down-regulated in CRC cell lines and tissue specimens. Ectopic miR-133a expression inhibited cell proliferation and cell migration. Stable overexpression of miR-133a was sufficient to suppress tumour growth and intrahepatic and pulmonary metastasis in vivo. Additional studies showed that miR-133a can target the 3' untranslated region (3'UTR) of LIM and SH3 protein 1 (LASP1) mRNA and suppress the expression of LASP1, which we identified in previous studies as a CRC-associated protein. In contrast to the phenotypes induced by miR-133a restoration, LASP1-induced cell proliferation and migration rescued miR-133a-mediated biological behaviours, as did LASP1 overexpression. Investigations of possible mechanisms underlying these behaviours revealed that miR-133a modulates the expression of key cellular molecules and participates in the MAPK pathway by inhibiting phosphorylation of ERK and MEK. miR-133a may play a key role in CRC genesis and metastasis, which suggests its potential role in the molecular therapy of cancer.
authors: Department of Medical Oncology, Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou, China.
authors: Hui
authors: H
authors: Wang
authors: Hongying
authors: H
authors: An
authors: Bin
authors: B
authors: Wang
authors: Qing
authors: Q
authors: Liao
authors: Weidong
authors: W
authors: Li
authors: Xuejun
authors: X
authors: Jin
authors: Shuzhong
authors: S
authors: Cui
authors: Yajie
authors: Y
authors: Zhang
authors: Yanqing
authors: Y
authors: Ding
authors: Liang
authors: L
authors: Zhao
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D020543:Proteome; D020928:Mitogen-Activated Protein Kinases
keywords: Colorectal carcinoma; MicroRNAs; Signal pathway; Tumour metastasis