microRNA-34a inhibits epithelial mesenchymal transition in human cholangiocarcinoma by targeting Smad4 through transforming growth factor-beta/Smad pathway.
microRNA-34a inhibits epithelial mesenchymal transition in human cholangiocarcinoma by targeting Smad4 through transforming growth factor-beta/Smad pathway.
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microRNA-34a 通过转化生长因子-β/Smad 通路靶向 Smad4，抑制人胆管癌的上皮间质转化。
DOI：
10.1186/s12885-015-1359-x
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发表时间：
2015-06-16
期刊：
影响因子：
3.8
通讯作者：
Wu D
中科院分区：
文献类型：
--
作者：
Qiao P;Li G;Bi W;Yang L;Yao L;Wu D
肝外胆管癌（EHCC）是消化系统罕见的恶性肿瘤之一，其特点是预后不良。 miRNA 的畸变已被证明与这种疾病的进展有关。在本研究中，我们评估了 miR-34a 对 EHCC 的表达和影响。通过定量实时聚合酶链反应（qRT-PCR）检测EHCC组织、邻近非肿瘤组织、患者正常胆管（NBD）标本和胆管癌（CC）细胞系中的miR-34a表达水平。进一步分析miR-34a与EHCC患者临床特征的关系。进一步使用计算搜索、功能性荧光素酶测定和蛋白质印迹来证明 CC 细胞中 miR-34a 的下游靶标。通过免疫组织化学方法鉴定 EHCC 患者中 miR-34a 的下游靶基因。进一步应用细胞形态、侵袭和迁移测定来确认 miR-34a 通过下游靶标的抗癌作用。与邻近非肿瘤组织和正常胆管组织相比，人EHCC组织和CC细胞系中miR-34a的表达显着降低。 miR-34a被发现与EHCC患者的迁移和侵袭相关。 Smad4在大多数EHCC患者中过度表达，并被进一步证明是miR-34a的下游靶标之一，参与EHCC的进展。此外，在体外，miR-34a的激活通过上皮间质转化（EMT）抑制TGF-β/Smad4信号通路的侵袭和迁移。综上所述，我们的结果表明，在人 EHCC 中，miR-34a 通过靶向 Smad4，通过 TGF-β/Smad 信号通路抑制 EMT，从而抑制侵袭和迁移。本文的在线版本 (doi:10.1186/s12885-015-1359-x) 包含补充材料，可供授权用户使用。
Extrahepatic Cholangiocarcinoma (EHCC) is one of the uncommon malignancies in the digestive system which is characterized by a poor prognosis. Aberrations of miRNAs have been shown involved in the progression of this disease. In this study, we evaluated the expression and effects of miR-34a on EHCC. miR-34a expression levels were detected in EHCC tissues, adjacent non-tumor tissues, normal bile duct (NBD) specimens of patients and cholangiocarcinoma (CC) cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Relationships between miR-34a with clinical characteristics of EHCC patients were further analyzed. Computational search, functional luciferase assay and western blot were further used to demonstrate the downstream target of miR-34a in CC cells. Immunohistochemistry was carried on to identify the downstream target gene of miR-34a in EHCC patients. Cell morphology, invasion and migration assays were further applied to confirm the anti-carcinogenic effects of miR-34a through the downstream target. miR-34a expression was significantly decreased in human EHCC tissues and CC cell lines when compared with the adjacent non-tumor tissues and normal bile duct tissues. miR-34a was found correlated with the migration and invasion in EHCC patients. Smad4 was over-expressed in most of the EHCC patients and was further demonstrated as one of the downstream targets of miR-34a, which was involved in the progression of EHCC. Moreover, activation of miR-34a suppressed invasion and migration through TGF-beta/Smad4 signaling pathway by epithelial-mesenchymal transition (EMT) in vitro. Taken together, our results suggest that miR-34a inhibits invasion and migration by targeting Smad4 to suppress EMT through TGF- beta/Smad signaling pathway in human EHCC. The online version of this article (doi:10.1186/s12885-015-1359-x) contains supplementary material, which is available to authorized users.
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影响因子：
2.9
作者：
Hirose A;Tajima H;Ohta T;Tsukada T;Okamoto K;Nakanuma S;Sakai S;Kinoshita J;Makino I;Furukawa H;Hayashi H;Nakamura K;Oyama K;Inokuchi M;Nakagawara H;Miyashita T;Takamura H;Ninomiya I;Kitagawa H;Fushida S;Fujimura T;Harada S
通讯作者：
Harada S
影响因子：
8.8
作者：
Nitta, T.;Mitsuhashi, T.;Hatanaka, Y.;Miyamoto, M.;Oba, K.;Tsuchikawa, T.;Suzuki, Y.;Hatanaka, K. C.;Hirano, S.;Matsuno, Y.
通讯作者：
Matsuno, Y.
影响因子：
3.7
作者：
An F;Yamanaka S;Allen S;Roberts LR;Gores GJ;Pawlik TM;Xie Q;Ishida M;Mezey E;Ferguson-Smith AC;Mori Y;Selaru FM
通讯作者：
Selaru FM
影响因子：
--
作者：
Li, Guodong;Thomas, Ann M.;Guo, Grace L.
通讯作者：
Guo, Grace L.
影响因子：
11.2
作者：
Kasinski AL;Slack FJ
通讯作者：
Slack FJ