机构:[1]Cancer Research Institute, Southern Medical University, Guangzhou, China[2]Department of Oncology, The First Hospital of Shijiazhuang, Shijiazhuang, China[3]Departmentof Oncology, Guangdong No. 2 Provincial People’s Hospital, Guangzhou, China[4]Department of Cardiovascular, Guangdong No. 2 Provincial People’s Hospital, Guangzhou,China[5]College of Biotechnology, Southern Medical University, Guangzhou, China[6]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou,China[7]Department of Anatomy, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou,China[8]Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China and 9Institute of Comparative Medicine & Laboratory Animal Center,Southern Medical University, Guangzhou, China
The miR-19 family (miR-19a and miR-19b-1) are key oncogenic components of the miR-17-92 cluster. Overexpression of miR-19 is strongly associated with cancer invasion and metastasis, and poor prognosis of cancer patients. However, the underlying mechanisms remain largely unknown. In the present study, we found that enforced expression of miR-19 including miR-19a and miR-19b-1 triggered epithelial-mesenchymal transition (EMT) of lung cancer cells A549 and HCC827 as shown by mesenchymal-like morphological conversion, downregulation of epithelial proteins (e.g., E-cadherin, ZO-1 (zona occludens 1), and α-catenin), upregulation of mesenchymal proteins (e.g., vimentin, fibronectin 1, N-cadherin, and snail1), formation of stress fibers, and reduced cell adhesion. In addition, enhanced migration and invasion were observed in the cancer cells A549 and HCC827 undergoing EMT. In contrast, silencing of endogenous miR-19 reversed EMT and reduced the migration and invasion abilities of A549 and HCC827 cells. DNA microarray results revealed significant changes of the expression of genes related to EMT, migration, and metastasis of miR-19-expressing A549 cells. Moreover, siRNA-mediated knockdown of PTEN, a target of miR-19, also resulted in EMT, migration, and invasion of A549 and HCC827 cells, suggesting that PTEN is involved in miR-19-induced EMT, migration and invasion of lung cancer cells. Furthermore, lung cancer cells undergoing EMT induced by miR-19 demonstrated reduced proliferation in vitro and in vivo, and enhanced resistance to apoptosis caused by TNF-α. Taken together, these findings suggest that miR-19 triggers EMT, which has an important role in the invasion and migration of lung cancer cells, accompanied by the reduced proliferation of cells.
基金:
National
Natural Science Foundation of China (Grant Nos 81172587 and 81372896 to
DX; Grant No. 81101535 to D-JL; Grant No. 61427807 to W-HH), the
Natural Science Foundation of Guangdong Province of China (Grant No.
2014A030313294 to DX; Grant No. 9151063101000015 to J-SJ), the Science
and Technology Planning Project of Guangdong Province of China (Grant Nos
2009B060300008 and 2013B060300013 to DX) and the major project funding
was from the R & D institutions of Fujain (2012I2004).
语种:
外文
PubmedID:
中科院(CAS)分区:
出版当年[2014]版:
大类|2 区医学
小类|2 区病理学3 区医学:研究与实验
最新[2025]版:
大类|2 区医学
小类|2 区医学:研究与实验2 区病理学
第一作者:
第一作者机构:[1]Cancer Research Institute, Southern Medical University, Guangzhou, China[2]Department of Oncology, The First Hospital of Shijiazhuang, Shijiazhuang, China
共同第一作者:
通讯作者:
通讯机构:[1]Cancer Research Institute, Southern Medical University, Guangzhou, China[8]Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China and 9Institute of Comparative Medicine & Laboratory Animal Center,Southern Medical University, Guangzhou, China[*1]Cancer Research Institute, Southern Medical University, Guangzhou 510515, China[*2]Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
推荐引用方式(GB/T 7714):
Li Jing,Yang Sheng,Yan Wen,et al.MicroRNA-19 triggers epithelial-mesenchymal transition of lung cancer cells accompanied by growth inhibition.[J].Laboratory investigation; a journal of technical methods and pathology.2015,95(9):1056-70.doi:10.1038/labinvest.2015.76.
APA:
Li Jing,Yang Sheng,Yan Wen,Yang Jie,Qin Yu-Juan...&Xiao Dong.(2015).MicroRNA-19 triggers epithelial-mesenchymal transition of lung cancer cells accompanied by growth inhibition..Laboratory investigation; a journal of technical methods and pathology,95,(9)
MLA:
Li Jing,et al."MicroRNA-19 triggers epithelial-mesenchymal transition of lung cancer cells accompanied by growth inhibition.".Laboratory investigation; a journal of technical methods and pathology 95..9(2015):1056-70