Lisha Chang1, Jingyue Wang1, Fuling Zhou1, Dali Wang1, Ruiying Chen1, Yunhe Zhang2, Jiang Zhang3. 1. Department of Neurology, North China University of Science and Technology Affiliated Hospital, No. 73, Jianshe South Road, Tangshan, 063000, Hebei Province, People's Republic of China. 2. Department of Neurosurgery, North China University of Science and Technology Affiliated Hospital, Tangshan, 063000, People's Republic of China. 3. Department of Neurology, North China University of Science and Technology Affiliated Hospital, No. 73, Jianshe South Road, Tangshan, 063000, Hebei Province, People's Republic of China. hebeizhangj@163.com.
Abstract
PURPOSE: Long noncoding RNAs (LncRNAs) are essential epigenetic regulators with critical roles in tumor initiation and malignant progression; however, the mechanism by which aberrantly expressed lncRNA RP11-84E24.3 regulates the pathogenesis of glioma is not fully understood. Here, we investigate the function of lncRNA RP11-84E24.3 in glioma onset and progression as well as identify a molecular pathway regulated by this lncRNA. METHODS: Differentially expressed lncRNAs related to glioma were identified. The aberrant expression of lncRNA RP11-84E24.3 was verified in samples from patients with glioma as well as glioma cell lines. The role of lncRNA RP11-8424.3 in proliferation, apoptosis, migration, and invasion was assessed using gain- and loss-of function approaches, EdU incorporation, flow cytometry, wound healing and Transwell invasion assays. Western blot analysis was utilized to examine the expression of proteins associated with epithelial-to-mesenchymal transition (EMT). The interaction between lncRNA RP11-84E24.3, TFAP2C and SNAI1 was confirmed using RNA pull-down, ChIP and luciferase reporter assays. RESULTS: LncRNA RP11-84E24.3 was up-regulated in both glioma tissues and cell lines. LncRNA RP11-84E24.3 overexpression enhanced the proliferation, migration and invasion of glioma cells while reducing apoptosis. This was associated with a decrease in E-cadherin expression and an increase in N-cadherin and Vimentin expression. LncRNA RP11-84E24.3 directly targeted TFAP2C protein, resulting in increased SNAI1 expression. Knockdown of TFAP2C or SNAI1 reversed the effects of lncRNA RP11-84E24.3 overexpression, while silencing lncRNA RP11-84E24.3 inhibited tumor formation of glioma cells in vivo. CONCLUSIONS: LncRNA RP11-84E24.3 increased SNAI1 expression by forming a complex with TFAP2C protein, promoting EMT in glioma cells and tumor formation.
PURPOSE: Long noncoding RNAs (LncRNAs) are essential epigenetic regulators with critical roles in tumor initiation and malignant progression; however, the mechanism by which aberrantly expressed lncRNA RP11-84E24.3 regulates the pathogenesis of glioma is not fully understood. Here, we investigate the function of lncRNA RP11-84E24.3 in glioma onset and progression as well as identify a molecular pathway regulated by this lncRNA. METHODS: Differentially expressed lncRNAs related to glioma were identified. The aberrant expression of lncRNA RP11-84E24.3 was verified in samples from patients with glioma as well as glioma cell lines. The role of lncRNA RP11-8424.3 in proliferation, apoptosis, migration, and invasion was assessed using gain- and loss-of function approaches, EdU incorporation, flow cytometry, wound healing and Transwell invasion assays. Western blot analysis was utilized to examine the expression of proteins associated with epithelial-to-mesenchymal transition (EMT). The interaction between lncRNA RP11-84E24.3, TFAP2C and SNAI1 was confirmed using RNA pull-down, ChIP and luciferase reporter assays. RESULTS: LncRNA RP11-84E24.3 was up-regulated in both glioma tissues and cell lines. LncRNA RP11-84E24.3 overexpression enhanced the proliferation, migration and invasion of glioma cells while reducing apoptosis. This was associated with a decrease in E-cadherin expression and an increase in N-cadherin and Vimentin expression. LncRNA RP11-84E24.3 directly targeted TFAP2C protein, resulting in increased SNAI1 expression. Knockdown of TFAP2C or SNAI1 reversed the effects of lncRNA RP11-84E24.3 overexpression, while silencing lncRNA RP11-84E24.3 inhibited tumor formation of glioma cells in vivo. CONCLUSIONS: LncRNA RP11-84E24.3 increased SNAI1 expression by forming a complex with TFAP2C protein, promoting EMT in glioma cells and tumor formation.
Authors: Hao Zhang; Ahmed Diab; Huitao Fan; Saravana Kumar Kailasam Mani; Ronald Hullinger; Philippe Merle; Ourania Andrisani Journal: Cancer Res Date: 2015-04-08 Impact factor: 12.701
Authors: Preetha Rajaraman; Beatrice S Melin; Zhaoming Wang; Roberta McKean-Cowdin; Dominique S Michaud; Sophia S Wang; Melissa Bondy; Richard Houlston; Robert B Jenkins; Margaret Wrensch; Meredith Yeager; Anders Ahlbom; Demetrius Albanes; Ulrika Andersson; Laura E Beane Freeman; Julie E Buring; Mary Ann Butler; Melissa Braganza; Tania Carreon; Maria Feychting; Sarah J Fleming; Susan M Gapstur; J Michael Gaziano; Graham G Giles; Goran Hallmans; Roger Henriksson; Judith Hoffman-Bolton; Peter D Inskip; Christoffer Johansen; Cari M Kitahara; Mark Lathrop; Chenwei Liu; Loic Le Marchand; Martha S Linet; Stefan Lonn; Ulrike Peters; Mark P Purdue; Nathaniel Rothman; Avima M Ruder; Marc Sanson; Howard D Sesso; Gianluca Severi; Xiao-Ou Shu; Matthias Simon; Meir Stampfer; Victoria L Stevens; Kala Visvanathan; Emily White; Alicja Wolk; Anne Zeleniuch-Jacquotte; Wei Zheng; Paul Decker; Victor Enciso-Mora; Brooke Fridley; Yu-Tang Gao; Matthew Kosel; Daniel H Lachance; Ching Lau; Terri Rice; Anthony Swerdlow; Joseph L Wiemels; John K Wiencke; Sanjay Shete; Yong-Bing Xiang; Yuanyuan Xiao; Robert N Hoover; Joseph F Fraumeni; Nilanjan Chatterjee; Patricia Hartge; Stephen J Chanock Journal: Hum Genet Date: 2012-08-11 Impact factor: 4.132