microRNA-182 targets special AT-rich sequence-binding protein 2 to promote colorectal cancer proliferation and metastasis.

microRNA-182 targets special AT-rich sequence-binding protein 2 to promote colorectal cancer proliferation and metastasis.
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microRNA-182靶向富含AT的特殊序列结合蛋白2促进结直肠癌增殖和转移

DOI:
10.1186/1479-5876-12-109
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发表时间:
2014-05-01
影响因子:
7.4
通讯作者:
Ding YQ
Ding YQ
中科院分区:
医学2区
文献类型:
--
作者:
Yang MH;Yu J;Jiang DM;Li WL;Wang S;Ding YQ

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Increasing evidence has revealed that microRNAs (miRNA) played a pivotal role in regulating cancer cell proliferation and metastasis. The deregulation of miR-182 has been identified in colorectal cancer (CRC). However, the role and mechanism of miR-182 in CRC have not been completely understood yet. The expression levels of miR-182 in CRC tissues and CRC cell lines were examined by performing stem-loop quantitative RT-PCR. The stable over-expression miR-182 cell lines and control cell lines were constructed by lentivirus infection. Subsequently, CCK-8 assay, plate colony formation assay, cell migration, invasion assay and experimental animal models were performed to detect the biological functions of miR-182 in vitro and in vivo. A luciferase reporter assay was conducted to confirm target associations. Western blot and immunohistochemical analysis were performed to examine the expression changes of molecular markers that are regulated by miR-182. We found that miR-182 expression is increased in CRC cells that originated from metastatic foci and human primary CRC tissues with lymph node metastases. The ectopic expression of miR-182 enhanced cell proliferation, invasion, and migration in vitro. Stable overexpression of miR-182 also facilitated tumor growth and metastasis in vivo too. Further research showed that miR-182 could directly target the 3’untranslated region (3’UTR) of SATB2 mRNA and subsequently repress both the mRNA and protein expressions of SATB2, which we identified in previous studies as a CRC metastasis-associated protein. Restoring SATB2 expression could reverse the effects of miR-182 on CRC cell proliferation and migration. Investigations of possible mechanisms underlying these behaviors induced by miR-182 revealed that miR-182 induced epithelial-mesenchymal transition (EMT) by modulating the expression of key cellular molecules in EMT. Our results illustrated that the up-regulation of miR-182 played a pivotal role in CRC tumorigenesis and metastasis, which suggesting a potential implication of miR-182 in the molecular therapy for CRC.
DOI: 10.1073/pnas.0808263106
发表时间: 2009-02-10
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五基因特征作为结直肠癌转移和生存的潜在预测因子
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