LEF1-AS1, a long non-coding RNA, promotes malignancy in glioblastoma
Jin Wang,1,* Xiaoyang Liu,1,* Changsheng Yan,2 Jie Liu,3 Songtao Wang,4 Yongzhi Hong,1 Aihua Gu,5,6 Peng Zhao1 1Department of Neurosurgery, 2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 3Xuzhou Maternity and Child Health Care Hospita...
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doaj-a3848a23bd874cf28581b8bad1f75e5c2020-11-24T23:33:04ZengDove Medical PressOncoTargets and Therapy1178-69302017-08-01Volume 104251426034461LEF1-AS1, a long non-coding RNA, promotes malignancy in glioblastomaWang JLiu XYan CLiu JWang SHong YGu AZhao PJin Wang,1,* Xiaoyang Liu,1,* Changsheng Yan,2 Jie Liu,3 Songtao Wang,4 Yongzhi Hong,1 Aihua Gu,5,6 Peng Zhao1 1Department of Neurosurgery, 2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 3Xuzhou Maternity and Child Health Care Hospital, Xuzhou Medical University, Xuzhou, 4Department of Intensive Care Unit, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 5State Key Laboratory of Reproductive Medicine, Institute of Toxicology, 6Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China *These authors contributed equally to this work Objectives: The long-noncoding RNAs (lncRNAs) are identified as new crucial regulators of diverse cellular processes in glioblastoma (GBM) tissues. However, the expression pattern and biological function of lncRNAs remain largely unknown. Here, for the first time, the effects of lncRNA lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) on GBM progression both in vitro and in vivo are investigated. Materials and methods: Expression profiles of LEF1-AS1 in GBM specimens were investigated by bioinformatics analyses. LEF1-AS1 expression in GBM tissues was detected using a quantitative polymerase chain reaction. LEF1-AS1 expression was inhibited by transfecting the LEF1-AS1-specific small interfering RNAs (siRNAs) and stable cell lines established were inhibited by transfecting si-LEF1-AS1 viruses. The Cell Counting Kit-8, ethynyl deoxyuridine, and colony formation assay were used to examine proliferation function. The flow cytometry detected cell-cycle change and apoptosis. Migration effects were detected by a Transwell assay. The tumor xenografts and immunohistochemistry were performed to evaluate tumor growth in vivo. Results: In this study, LEF1-AS1 expression was found significantly upregulated in GBM specimens compared with normal tissues. The 5-year overall survival in GBM patients from The Cancer Genome Atlas with high expression of LEF1-AS1 was inferior to that with low expression. It was confirmed that expression of LEF1-AS1 was higher in GBM tissues than normal ones. Knockdown of LEF1-AS1 significantly inhibited the malignancy of GBM cells, including proliferation and invasion, and promoted cell apoptosis. The result of Western blot assays indicated that knockdown of LEF1-AS1-mediated tumor suppression in GBM cells may be via the reduction of ERK and Akt/mTOR signaling activities. Finally, the in vivo experiment also demonstrated that knockdown LEF1-AS1 inhibited the growth-promoting effect of LEF1-AS1 of U87 cells. Conclusion: Our result indicated that lncRNA LEF1-AS1 acts as an oncogene in GBM and may be a pivotal target for this disease. Keywords: lncRNA, LEF1-AS1, glioblastoma, proliferation, invasion, apoptosishttps://www.dovepress.com/lef1-as1-a-long-non-coding-rna-promotes-malignancy-in-glioblastoma-peer-reviewed-article-OTTlincRNALEF1-AS1glioblastomaproliferationinvasionapoptosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wang J Liu X Yan C Liu J Wang S Hong Y Gu A Zhao P |
spellingShingle |
Wang J Liu X Yan C Liu J Wang S Hong Y Gu A Zhao P LEF1-AS1, a long non-coding RNA, promotes malignancy in glioblastoma OncoTargets and Therapy lincRNA LEF1-AS1 glioblastoma proliferation invasion apoptosis |
author_facet |
Wang J Liu X Yan C Liu J Wang S Hong Y Gu A Zhao P |
author_sort |
Wang J |
title |
LEF1-AS1, a long non-coding RNA, promotes malignancy in glioblastoma |
title_short |
LEF1-AS1, a long non-coding RNA, promotes malignancy in glioblastoma |
title_full |
LEF1-AS1, a long non-coding RNA, promotes malignancy in glioblastoma |
title_fullStr |
LEF1-AS1, a long non-coding RNA, promotes malignancy in glioblastoma |
title_full_unstemmed |
LEF1-AS1, a long non-coding RNA, promotes malignancy in glioblastoma |
title_sort |
lef1-as1, a long non-coding rna, promotes malignancy in glioblastoma |
publisher |
Dove Medical Press |
series |
OncoTargets and Therapy |
issn |
1178-6930 |
publishDate |
2017-08-01 |
description |
Jin Wang,1,* Xiaoyang Liu,1,* Changsheng Yan,2 Jie Liu,3 Songtao Wang,4 Yongzhi Hong,1 Aihua Gu,5,6 Peng Zhao1 1Department of Neurosurgery, 2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 3Xuzhou Maternity and Child Health Care Hospital, Xuzhou Medical University, Xuzhou, 4Department of Intensive Care Unit, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 5State Key Laboratory of Reproductive Medicine, Institute of Toxicology, 6Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China *These authors contributed equally to this work Objectives: The long-noncoding RNAs (lncRNAs) are identified as new crucial regulators of diverse cellular processes in glioblastoma (GBM) tissues. However, the expression pattern and biological function of lncRNAs remain largely unknown. Here, for the first time, the effects of lncRNA lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) on GBM progression both in vitro and in vivo are investigated. Materials and methods: Expression profiles of LEF1-AS1 in GBM specimens were investigated by bioinformatics analyses. LEF1-AS1 expression in GBM tissues was detected using a quantitative polymerase chain reaction. LEF1-AS1 expression was inhibited by transfecting the LEF1-AS1-specific small interfering RNAs (siRNAs) and stable cell lines established were inhibited by transfecting si-LEF1-AS1 viruses. The Cell Counting Kit-8, ethynyl deoxyuridine, and colony formation assay were used to examine proliferation function. The flow cytometry detected cell-cycle change and apoptosis. Migration effects were detected by a Transwell assay. The tumor xenografts and immunohistochemistry were performed to evaluate tumor growth in vivo. Results: In this study, LEF1-AS1 expression was found significantly upregulated in GBM specimens compared with normal tissues. The 5-year overall survival in GBM patients from The Cancer Genome Atlas with high expression of LEF1-AS1 was inferior to that with low expression. It was confirmed that expression of LEF1-AS1 was higher in GBM tissues than normal ones. Knockdown of LEF1-AS1 significantly inhibited the malignancy of GBM cells, including proliferation and invasion, and promoted cell apoptosis. The result of Western blot assays indicated that knockdown of LEF1-AS1-mediated tumor suppression in GBM cells may be via the reduction of ERK and Akt/mTOR signaling activities. Finally, the in vivo experiment also demonstrated that knockdown LEF1-AS1 inhibited the growth-promoting effect of LEF1-AS1 of U87 cells. Conclusion: Our result indicated that lncRNA LEF1-AS1 acts as an oncogene in GBM and may be a pivotal target for this disease. Keywords: lncRNA, LEF1-AS1, glioblastoma, proliferation, invasion, apoptosis |
topic |
lincRNA LEF1-AS1 glioblastoma proliferation invasion apoptosis |
url |
https://www.dovepress.com/lef1-as1-a-long-non-coding-rna-promotes-malignancy-in-glioblastoma-peer-reviewed-article-OTT |
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