MicroRNA-145 inhibits lung cancer cell metastasis

MicroRNA-145 inhibits lung cancer cell metastasis
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DOI:
10.3892/mmr.2014.3036
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发表时间:
2015-04-01
影响因子:
3.4
通讯作者:
Shi, Tian-Sheng
Shi, Tian-Sheng
中科院分区:
医学4区
文献类型:
--
作者:
Ling, Dong-Jin;Chen, Zhong-Shu;Shi, Tian-Sheng

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先前的研究已经确定了多种microRNAs (miRNAs)在癌症进展,特别是肿瘤侵袭和转移中发挥重要作用。据报道,miR-145的下调发生在各种类型的人类癌症中;然而,miR-145在肺癌转移中的作用及其潜在的作用机制仍有待阐明。本研究旨在探讨miR-145对A549人肺腺癌细胞转移和上皮-间质转化(EMT)的影响。此外,我们还研究了miR-145调控EMT的潜在机制。将miR-145 mimic转染到A549细胞中;然后进行细胞侵袭和粘附试验以研究细胞转移,并采用western blot分析检测EMT标志物的表达。为了进一步研究miR-145调控EMT的潜在机制,我们进行了荧光素酶报告基因检测,以确定miR-145是否靶向Oct4。此外,用小发夹RNA-Oct4转染A549细胞后,检测Wnt3a和-catenin的表达。据我们所知,本研究的结果首次证明miR-145通过靶向Oct4介导的Wnt/-catenin信号通路抑制肺癌细胞转移和EMT。
Previous studies have identified a variety of microRNAs (miRNAs) that have important roles in cancer progression, particularly in tumor invasion and metastasis. Downregulation of miR-145 was reported to occur in various types of human cancer; however, the role of miR-145 in lung cancer metastasis and its potential mechanisms of action remain to be elucidated. The present study aimed to investigate the effects of miR-145 on metastasis and epithelial-mesenchymal transition (EMT) in A549 human lung adenocarcinoma cells. In addition, the underlying mechanisms by which miR-145 regulates EMT were examined. The miR-145 mimic was transfected into A549 cells; cell invasion and adhesion assays were then performed in order to investigate cell metastasis, and western blot analysis was used to examine the expression of EMT markers. In order to further examine the underlying mechanisms by which miR-145 regulates EMT, a luciferase reporter assay was performed to determine whether miR-145 targeted Oct4. In addition, the expression of Wnt3a and -catenin in A549 cells was measured following transfection with small hairpin RNA-Oct4. To the best of our knowledge, the results of the present study demonstrated for the first time, that miR-145 inhibited lung cancer cell metastasis and EMT via targeting the Oct4 mediated Wnt/-catenin signaling pathway.