miR-29b suppresses tumor growth and metastasis in colorectal cancer via downregulating Tiam1 expression and inhibiting epithelial-mesenchymal transition.
miR-29b suppresses tumor growth and metastasis in colorectal cancer via downregulating Tiam1 expression and inhibiting epithelial-mesenchymal transition.
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miR-29b通过下调TIAM1表达并抑制上皮 - 间质转变，从而抑制结直肠癌的肿瘤生长和转移。
DOI：
10.1038/cddis.2014.304
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发表时间：
2014-07-17
影响因子：
9
通讯作者：
Zhao, L.
中科院分区：
文献类型：
--
作者：
Wang, B.;Li, W.;Liu, H.;Yang, L.;Liao, Q.;Cui, S.;Wang, H.;Zhao, L.
最近，miR-29 b在结直肠癌（CRC）发展中的作用似乎存在争议。miR-29 b在结直肠癌中的表达及功能尚不清楚。我们发现miR-29 b的表达降低通常发生在CRC细胞系和组织样本中。体外功能丧失和获得测定揭示了miR-29 b对细胞增殖和迁移的抑制作用。内源性miR-29 b过表达足以抑制小鼠的攻击性行为表型。蛋白质组学分析表明，miR-29 b参与了多种关键的生物学过程。此外，miR-29 b还介导了上皮-间质转化（EMT）的抑制以及丝裂原活化蛋白激酶和磷脂酰肌醇-4，5-二磷酸3-激酶/AKT信号转导通路的失活。进一步的研究发现T淋巴瘤侵袭和转移1（Tiam 1）被确定为miR-29 b的直接靶点。与miR-29 b修复诱导的表型相反，Tiam 1诱导的细胞增殖和迁移部分挽救了miR-29 b介导的生物学行为。我们的研究结果表明，miR-29 b作为一种抑制剂在CRC进展中起着关键作用，这表明其在晚期CRC患者的分子治疗中具有潜在的作用。
Recently, the role of miR-29b in colorectal carcinoma (CRC) development appears to be controversial. Until now, the expression and function of miR-29b in CRC have not been clarified clearly. We showed that decreased expression of miR-29b usually occurred in CRC cell lines and tissue samples. Loss- and gain-of-function assays in vitro revealed suppressive effects of miR-29b on cell proliferation and migration. Endogenous overexpression of miR-29b was sufficient to suppress aggressive behavioral phenotypes in mice. Proteomic analysis showed that miR-29b involved in integrate several key biological processes. In addition, miR-29b mediated the inhibition of epithelial–mesenchymal transition (EMT) and the inactivation of mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT signal transduction pathway. Further studies found that T lymphoma invasion and metastasis 1 (Tiam1) was identified as a direct target of miR-29b. In contrast to the phenotypes induced by miR-29b restoration, Tiam1-induced cell proliferation and migration partly rescued miR-29b-mediated biological behaviors. Our results illustrated that miR-29b as a suppressor has a critical role in CRC progression, which suggests its potential role in the molecular therapy of patients with advanced CRC.
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影响因子：
8
作者：
Uematsu, K;He, BA;Jablons, DM
通讯作者：
Jablons, DM
影响因子：
3.1
作者：
Ioshikhes, Ilya;Roy, Sashwati;Sen, Chandan K.
通讯作者：
Sen, Chandan K.
影响因子：
5.7
作者：
Ru, Peng;Steele, Robert;Ray, Ratna B.
通讯作者：
Ray, Ratna B.
DOI：
10.1111/igc.0b013e3181a48cf9
发表时间：
2009-05-01
影响因子：
4.8
作者：
Flavin, Richard;Smyth, Paul;O'Leary, John J.
通讯作者：
O'Leary, John J.
microRNA参与癌症干细胞的自我更新和分化。
影响因子：
8.2
作者：
Wang, Zheng-ming;Du, Wen-jun;Piazza, Gary A.;Xi, Yaguang
通讯作者：
Xi, Yaguang