Tumor suppressor miR-1 restrains epithelial-mesenchymal transition and metastasis of colorectal carcinoma via the MAPK and PI3K/AKT pathway

Journal of Translational Medicine

Liang Zhao¹  Yanqing Ding¹  Guanhua Zhang³  Hui Wang²  Yue Zhang³  Lijun Xu³ 

[1] Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China;Department of Medical Oncology, Affiliated Tumor Hospital of Guangzhou Medical University, Guangzhou, China;Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China

关键词: Gene therapy;    Proteomics;    Signal pathway;    LIM and SH3 protein 1;    Tumor metastasis;    MicroRNA;    Colorectal carcinoma;   

Others  :  1148221
DOI  :  10.1186/s12967-014-0244-8

 received in 2014-07-11, accepted in 2014-08-26,  发布年份 2014

【 摘 要 】

Aberrant expression of miR-1 has been implicated in various cancers. However, the mechanisms underlying the role of miR-1 in CRC progression still have not been clarified clearly. Here, we showed the decreased expression of miR-1 in colorectal carcinoma (CRC) tissues and cell lines. Ectopic introduction of miR-1 suppressed cell proliferation and migration, whereas miR-1 inhibitor performed contrary functions in CRC cells. Stable overexpression of miR-1 was sufficient to inhibit tumor growth and homing capacity in vivo. Proteomic analysis revealed that miR-1 modulated the expression of key cellular molecules and involved in the MAPK and PI3K/AKT pathways by inhibiting phosphorylation of ERK and AKT. Meanwhile, miR-1 also reversed epithelial¿mesenchymal transition (EMT), which played a pivotal role in the initiation of metastasis. Further studies found that miR-1 can target the 3' untranslated region (3'UTR) of LIM and SH3 protein 1 (LASP1) mRNA and suppress the expression of LASP1, identified as a CRC-associated protein. In contrast to the phenotypes induced by miR-1 restoration, LASP1-induced cell proliferation and migration partly rescued miR-1-mediated biological behaviors. Our results illustrated that miR-1 play a critical role in CRC progression, which suggests its potential role in the molecular therapy of cancer.

【 授权许可】

   
2014 Xu et al.; licensee BioMed Central Ltd.

【 图 表 】

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