MicroRNA-196b Inhibits Cell Growth and Metastasis of Lung Cancer Cells by Targeting Runx2 (Publication with Expression of Concern. See vol. 55, pg. 238, 2021)
MicroRNA-196b Inhibits Cell Growth and Metastasis of Lung Cancer Cells by Targeting Runx2 (Publication with Expression of Concern. See vol. 55, pg. 238, 2021)
复制标题
DOI：
10.1159/000481559
复制
发表时间：
2017-01-01
影响因子：
--
通讯作者：
Hua, Shucheng
中科院分区：
文献类型：
--
作者：
Bai, Xiaoxue;Meng, Lin;Hua, Shucheng
背景/目的：肺癌是全球癌症相关死亡的最常见原因之一。包括miR-196 b在内的几种microRNA（miRNAs）在不同癌症中的作用已经确定。本研究旨在探讨miR-196 b在肺癌中的作用及其可能机制。方法：将miR-196 b模拟物、miR-196 b抑制剂及相应对照转染人肺癌细胞系A549。然后依次评估过表达或抑制miR-196 b的A549肺癌细胞的细胞活力、迁移、侵袭和凋亡。接下来，进行双荧光素酶活性测定以澄清Runx 2是否是miR-196 b的直接靶标。Western blot检测上皮间质转化（EMT）相关因子、PI 3 K/AKT/GSK 3 β、Smad和JNK通路的表达。结果：miR-196 b在A549、H1650和H1299细胞系中的表达明显低于WI-38和HEL-1细胞系。过表达miR-196 b可抑制A549细胞的存活、迁移、侵袭和诱导凋亡，并抑制TGF-β诱导的EMT过程。此外，Runx 2是miR-196 b的假定靶点，Runx 2沉默显著增加细胞凋亡，并消除miR-196 b抑制对细胞活力、迁移和侵袭的促进作用。最后，miR-196 b还通过下调Runx 2使PI 3 K/AKT/GSK 3 β、Smad和JNK通路失活来介导其作用。结论：miR-196 b是一种肿瘤抑制因子，可通过靶向Runx 2抑制肺癌细胞的生长和转移。这些发现为肺癌的治疗提供了进一步的依据。(C)2017作者（s）由S. Karger AG，巴塞尔
Background/Aims: Lung cancer is one of the most common causes of cancer related deaths worldwide. The role of several microRNAs (miRNAs) including miR-196b in different cancers has already been established. The study was aimed to explore the role of miR-196b in lung cancer and its possible underlying mechanism. Methods: Human lung cancer cell line A549 was transfected with miR-196b mimic, miR-196b inhibitor and corresponding controls. Then cell viability, migration, invasion, and apoptosis of A549 lung cancer cells either with overexpression or with suppression of miR-196b were estimated sequentially. Next, dual luciferase activity assay was performed to clarify whether Runx2 was a direct target of miR-196b. Finally, the expressions of main factors associated with epithelial mesenchymal transition (EMT), PI3K/AKT/GSK3 beta, Smad, and JNK pathways were detected by western blot. Results: MiR-196b expression was significantly decreased in A549, H1650 and H1299 cell lines compared with in WI-38 and HEL-1 cell lines. Overexpression of miR-196b suppressed cell viability, migration, invasion, and induced apoptosis as well as inhibited TGF-beta induced EMT process in A549 cells. In addition, Runx2 was a putative target of miR-196b, and Runx2 silence remarkably increased cell apoptosis and abolished the promotive effects of miR-196b suppression on cell viability, migration and invasion. Finally, miR-196b also mediated its action by inactivation of PI3K/AKT/GSK3 beta, Smad, and JNK pathways by down-regulation of Runx2. Conclusion: MiR-196b functions as a tumor suppressor that inhibited cell growth and metastasis of lung cancer cells by targeting Runx2. These findings provided further evidences for treatment of lung cancer. (C) 2017 The Author(s) Published by S. Karger AG, Basel