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Eur J Cancer. 2013 Dec;49(18):3924-35. doi: 10.1016/j.ejca.2013.07.149. Epub 2013 Aug 19.

miR-133a represses tumour growth and metastasis in colorectal cancer by targeting LIM and SH3 protein 1 and inhibiting the MAPK pathway.

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  • 1Department of Medical Oncology, Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou, China.

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.

KEYWORDS:

Colorectal carcinoma; MicroRNAs; Signal pathway; Tumour metastasis

PMID:
23968734
DOI:
10.1016/j.ejca.2013.07.149
[PubMed - indexed for MEDLINE]
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