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Published in: Cancer Cell International 1/2017

Open Access 01-12-2017 | Primary Research

Overexpression of lncRNA HOXA11-AS promotes cell epithelial–mesenchymal transition by repressing miR-200b in non-small cell lung cancer

Authors: Jian-Hui Chen, Li-Yang Zhou, Suo Xu, Yu-Long Zheng, Yu-Feng Wan, Cheng-Ping Hu

Published in: Cancer Cell International | Issue 1/2017

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Abstract

Background

Recent studies have verified that long noncoding RNAs (lncRNAs) involved in many biological functions and play crucial roles in human cancers progression, the study aimed to detect the association between long non-coding RNA HOXA11-AS and epithelial–mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC).

Methods

The lncRNA HOXA11-AS expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) assays in 78 paired of tumor tissue and adjacent normal tissue samples in NSCLC patients. Kaplan–Meier survival curves and log-rank test was used to examine the association between lncRNA HOXA11-AS expression and the over survival time in NSCLC patients. Transwell invasion assay was performed to detect the cell invasion ability. QRT-PCR and western-blot analysis detected the mRNA and protein expression of EMT related transcription factors ZEB1/ZEB2, Snail1/2 and EMT marker E-cadherin and N-cadherin in NSCLC cells. RIP and Chromatin immunoprecipitation assays were performed to analyze the association between lncRNA HOXA11-AS and miR-200b expression in NSCLC cells.

Results

The lncRNA HOXA11-AS expression levels were significantly higher in NSCLC tissues compared with adjacent normal tissues and higher HOXA11-AS expression levels had a poor prognosis in NSCLC patients. Furthermore, knockdown of lncRNA HOXA11-AS in A549 and H1299 cells dramatically inhibited cell invasive abilities. Besides, the transcription levels and protein levels of EMT related transcription factors ZEB1/ZEB2, Snail1/2, and EMT maker N-cadherin were down-regulated after lncRNA HOXA11-AS was knocked down, but the mRNA and protein expression levels of EMT maker E-cadherin was increasing in A549 and H1299 cells. The mechanistic findings showed demonstrated that HOXA11-AS interacted with EZH2 and DNMT1 and recruited them to the miR-200b promoter regions to repress miR-200b expression in NSCLC cells, which promoted cell EMT in NSCLC.

Conclusions

Our results showed that up-regulation of lncRNA HOXA11-AS predicted a poor prognosis and lncRNA HOXA11-AS promoted cell epithelial–mesenchymal transition (EMT) by inhibiting miR-200b expression in NSCLC.
Literature
1.
go back to reference Verdecchia A, Francisci S, Brenner H, Gatta G, Micheli A, Mangone L, Kunkler I, EUROCARE-4 Working Group. Recent cancer survival in Europe: a 2000–02 period analysis of EUROCARE-4 data. Lancet Oncol. 2007;8:784–96.CrossRefPubMed Verdecchia A, Francisci S, Brenner H, Gatta G, Micheli A, Mangone L, Kunkler I, EUROCARE-4 Working Group. Recent cancer survival in Europe: a 2000–02 period analysis of EUROCARE-4 data. Lancet Oncol. 2007;8:784–96.CrossRefPubMed
2.
go back to reference Sève P, Reiman T, Dumontet C. The role of betaIII tubulin in predicting chemoresistance in non-small cell lung cancer. Lung Cancer. 2010;67:136–43.CrossRefPubMed Sève P, Reiman T, Dumontet C. The role of betaIII tubulin in predicting chemoresistance in non-small cell lung cancer. Lung Cancer. 2010;67:136–43.CrossRefPubMed
3.
go back to reference Zhang Y, He RQ, Dang YW, Zhang XL, Wang X, Huang SN, Huang WT, Jiang MT, Gan XN, Xie Y, Li P, Luo DZ, Chen G, Gan TQ. Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells. Cancer Cell Int. 2016;16:89.CrossRefPubMedPubMedCentral Zhang Y, He RQ, Dang YW, Zhang XL, Wang X, Huang SN, Huang WT, Jiang MT, Gan XN, Xie Y, Li P, Luo DZ, Chen G, Gan TQ. Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells. Cancer Cell Int. 2016;16:89.CrossRefPubMedPubMedCentral
4.
go back to reference Chen J, Wang R, Zhang K, Chen LB.Long non-coding RNAs in non-small cell lung cancer as biomarkers and therapeutic targets. J Cell Mol Med. 2014;18:2425–36. Chen J, Wang R, Zhang K, Chen LB.Long non-coding RNAs in non-small cell lung cancer as biomarkers and therapeutic targets. J Cell Mol Med. 2014;18:2425–36.
5.
go back to reference Chen J, Fu Z, Ji C, Gu P, Xu P, Yu N, Kan Y, Wu X, Shen R, Shen Y. Systematic gene microarray analysis of the lncRNA expression profiles in human uterine cervix carcinoma. Biomed Pharmacother. 2015;72:83–90.CrossRefPubMed Chen J, Fu Z, Ji C, Gu P, Xu P, Yu N, Kan Y, Wu X, Shen R, Shen Y. Systematic gene microarray analysis of the lncRNA expression profiles in human uterine cervix carcinoma. Biomed Pharmacother. 2015;72:83–90.CrossRefPubMed
6.
7.
go back to reference Ma G, Tang M, Wu Y, Xu X, Pan F, Xu R. LncRNAs and miRNAs: potential biomarkers and therapeutic targets for prostate cancer. Am J Transl Res. 2016;8:5141–50.PubMedPubMedCentral Ma G, Tang M, Wu Y, Xu X, Pan F, Xu R. LncRNAs and miRNAs: potential biomarkers and therapeutic targets for prostate cancer. Am J Transl Res. 2016;8:5141–50.PubMedPubMedCentral
8.
go back to reference Fu X, Li H, Liu C, Hu B, Li T, Wang Y. Long noncoding RNA AK126698 inhibits proliferation and migration of non-small cell lung cancer cells by targeting Frizzled-8 and suppressing Wnt/beta-catenin signaling pathway. Onco Targets Ther. 2016;9:3815–27.CrossRefPubMedPubMedCentral Fu X, Li H, Liu C, Hu B, Li T, Wang Y. Long noncoding RNA AK126698 inhibits proliferation and migration of non-small cell lung cancer cells by targeting Frizzled-8 and suppressing Wnt/beta-catenin signaling pathway. Onco Targets Ther. 2016;9:3815–27.CrossRefPubMedPubMedCentral
9.
go back to reference Wu Y, Lyu H, Liu H, Shi X, Song Y, Liu B. Downregulation of the long noncoding RNA GAS5-AS1 contributes to tumor metastasis in non-small cell lung cancer. Sci Rep. 2016;6:31093.CrossRefPubMedPubMedCentral Wu Y, Lyu H, Liu H, Shi X, Song Y, Liu B. Downregulation of the long noncoding RNA GAS5-AS1 contributes to tumor metastasis in non-small cell lung cancer. Sci Rep. 2016;6:31093.CrossRefPubMedPubMedCentral
10.
go back to reference Sang Y, Zhou F, Wang D, Bi X, Liu X, Hao Z, Li Q, Zhang W. Up-regulation of long non-coding HOTTIP functions as an oncogene by regulating HOXA13 in non-small cell lung cancer. Am J Transl Res. 2016;8:2022–32.PubMedPubMedCentral Sang Y, Zhou F, Wang D, Bi X, Liu X, Hao Z, Li Q, Zhang W. Up-regulation of long non-coding HOTTIP functions as an oncogene by regulating HOXA13 in non-small cell lung cancer. Am J Transl Res. 2016;8:2022–32.PubMedPubMedCentral
11.
go back to reference Shi X, Ma C, Zhu Q, Yuan D, Sun M, Gu X, Wu G, Lv T, Song Y. Upregulation of long intergenic noncoding RNA 00673 promotes tumor proliferation via LSD1 interaction and repression of NCALD in non-small-cell lung cancer. Oncotarget. 2016;7:25558–75.PubMedPubMedCentral Shi X, Ma C, Zhu Q, Yuan D, Sun M, Gu X, Wu G, Lv T, Song Y. Upregulation of long intergenic noncoding RNA 00673 promotes tumor proliferation via LSD1 interaction and repression of NCALD in non-small-cell lung cancer. Oncotarget. 2016;7:25558–75.PubMedPubMedCentral
12.
go back to reference Richards EJ, Permuth-Wey J, Li Y, Chen YA, Coppola D, Reid BM, Lin HY, Teer JK, Berchuck A, Birrer MJ, Lawrenson K, Monteiro AN, Schildkraut JM, Goode EL, Gayther SA, Sellers TA, Cheng JQ. A functional variant in HOXA11-AS, a novel long non-coding RNA, inhibits the oncogenic phenotype of epithelial ovarian cancer. Oncotarget. 2015;6:34745–57.PubMedPubMedCentral Richards EJ, Permuth-Wey J, Li Y, Chen YA, Coppola D, Reid BM, Lin HY, Teer JK, Berchuck A, Birrer MJ, Lawrenson K, Monteiro AN, Schildkraut JM, Goode EL, Gayther SA, Sellers TA, Cheng JQ. A functional variant in HOXA11-AS, a novel long non-coding RNA, inhibits the oncogenic phenotype of epithelial ovarian cancer. Oncotarget. 2015;6:34745–57.PubMedPubMedCentral
13.
go back to reference Wang Q, Zhang J, Liu Y, Zhang W, Zhou J, Duan R, Pu P, Kang C, Han L. A novel cell cycle-associated lncRNA, HOXA11-AS, is transcribed from the 5-prime end of the HOXA transcript and is a biomarker of progression in glioma. Cancer Lett. 2016;373:251–9.CrossRefPubMed Wang Q, Zhang J, Liu Y, Zhang W, Zhou J, Duan R, Pu P, Kang C, Han L. A novel cell cycle-associated lncRNA, HOXA11-AS, is transcribed from the 5-prime end of the HOXA transcript and is a biomarker of progression in glioma. Cancer Lett. 2016;373:251–9.CrossRefPubMed
14.
go back to reference Sun M, Nie F, Wang Y, Zhang Z, Hou J, He D, Xie M, Xu L, De W, Wang Z, Wang J. LncRNA HOXA11-AS promotes proliferation and invasion of gastric cancer by scaffolding the chromatin modification factors PRC2, LSD1, and DNMT1. Cancer Res. 2016;76:6299–310.CrossRefPubMed Sun M, Nie F, Wang Y, Zhang Z, Hou J, He D, Xie M, Xu L, De W, Wang Z, Wang J. LncRNA HOXA11-AS promotes proliferation and invasion of gastric cancer by scaffolding the chromatin modification factors PRC2, LSD1, and DNMT1. Cancer Res. 2016;76:6299–310.CrossRefPubMed
15.
go back to reference Li T, Xu C, Cai B, Zhang M, Gao F, Gan J. Expression and clinicopathological significance of the lncRNA HOXA11-AS in colorectal cancer. Oncol Lett. 2016;12(5):4155–60.PubMedPubMedCentral Li T, Xu C, Cai B, Zhang M, Gao F, Gan J. Expression and clinicopathological significance of the lncRNA HOXA11-AS in colorectal cancer. Oncol Lett. 2016;12(5):4155–60.PubMedPubMedCentral
16.
go back to reference Yuan X, Wu H, Han N, Xu H, Chu Q, Yu S, Chen Y, Wu K. Notch signaling and EMT in non-small cell lung cancer: biological significance and therapeutic application. J Hematol Oncol. 2014;7:87.CrossRefPubMedPubMedCentral Yuan X, Wu H, Han N, Xu H, Chu Q, Yu S, Chen Y, Wu K. Notch signaling and EMT in non-small cell lung cancer: biological significance and therapeutic application. J Hematol Oncol. 2014;7:87.CrossRefPubMedPubMedCentral
17.
go back to reference Sui CJ, Zhou YM, Shen WF, Dai BH, Lu JJ, Zhang MF, Yang JM. Long noncoding RNA GIHCG promotes hepatocellular carcinoma progression through epigenetically regulating miR-200b/a/429. J Mol Med (Berl). 2016;94:1281–96.CrossRef Sui CJ, Zhou YM, Shen WF, Dai BH, Lu JJ, Zhang MF, Yang JM. Long noncoding RNA GIHCG promotes hepatocellular carcinoma progression through epigenetically regulating miR-200b/a/429. J Mol Med (Berl). 2016;94:1281–96.CrossRef
19.
go back to reference Kim HJ, Eoh KJ, Kim LK, Nam EJ, Yoon SO, Kim KH, Lee JK, Kim SW, Kim YT. The long noncoding RNA HOXA11 antisense induces tumor progression and stemness maintenance in cervical cancer. Oncotarget. 2016;7:83001–16.PubMedPubMedCentral Kim HJ, Eoh KJ, Kim LK, Nam EJ, Yoon SO, Kim KH, Lee JK, Kim SW, Kim YT. The long noncoding RNA HOXA11 antisense induces tumor progression and stemness maintenance in cervical cancer. Oncotarget. 2016;7:83001–16.PubMedPubMedCentral
20.
go back to reference Sun M, Liu XH, Wang KM, Nie FQ, Kong R, Yang JS, Xia R, Xu TP, Jin FY, Liu ZJ, Chen JF, Zhang EB, De W, Wang ZX. Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial–mesenchymal transition. Mol Cancer. 2014;13:68.CrossRefPubMedPubMedCentral Sun M, Liu XH, Wang KM, Nie FQ, Kong R, Yang JS, Xia R, Xu TP, Jin FY, Liu ZJ, Chen JF, Zhang EB, De W, Wang ZX. Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial–mesenchymal transition. Mol Cancer. 2014;13:68.CrossRefPubMedPubMedCentral
21.
go back to reference Shen L, Chen L, Wang Y, Jiang X, Xia H, Zhuang Z. Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial–mesenchymal transition in lung cancer. J Neurooncol. 2015;121:101–8.CrossRefPubMed Shen L, Chen L, Wang Y, Jiang X, Xia H, Zhuang Z. Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial–mesenchymal transition in lung cancer. J Neurooncol. 2015;121:101–8.CrossRefPubMed
22.
go back to reference Miao L, Huang Z, Zengli Z, Li H, Chen Q, Yao C, Cai H, Xiao Y, Xia H, Wang Y. Loss of long noncoding RNA FOXF1-AS1 regulates epithelial–mesenchymal transition, stemness and metastasis of non-small cell lung cancer cells. Oncotarget. 2016;7:68339–49.PubMedPubMedCentral Miao L, Huang Z, Zengli Z, Li H, Chen Q, Yao C, Cai H, Xiao Y, Xia H, Wang Y. Loss of long noncoding RNA FOXF1-AS1 regulates epithelial–mesenchymal transition, stemness and metastasis of non-small cell lung cancer cells. Oncotarget. 2016;7:68339–49.PubMedPubMedCentral
23.
go back to reference Cheng YX, Zhang QF, Hong L, Pan F, Huang JL, Li BS, Hu M. MicroRNA-200b suppresses cell invasion and metastasis by inhibiting the epithelial–mesenchymal transition in cervical carcinoma. Mol Med Rep. 2016;13:3155–60.PubMed Cheng YX, Zhang QF, Hong L, Pan F, Huang JL, Li BS, Hu M. MicroRNA-200b suppresses cell invasion and metastasis by inhibiting the epithelial–mesenchymal transition in cervical carcinoma. Mol Med Rep. 2016;13:3155–60.PubMed
24.
go back to reference Eggers JC, Martino V, Reinbold R, Schäfer SD, Kiesel L, Starzinski-Powitz A, Schüring AN, Kemper B, Greve B, Götte M. microRNA miR-200b affects proliferation, invasiveness and stemness of endometriotic cells by targeting ZEB1, ZEB2 and KLF4. Reprod Biomed Online. 2016;32:434–45.CrossRefPubMed Eggers JC, Martino V, Reinbold R, Schäfer SD, Kiesel L, Starzinski-Powitz A, Schüring AN, Kemper B, Greve B, Götte M. microRNA miR-200b affects proliferation, invasiveness and stemness of endometriotic cells by targeting ZEB1, ZEB2 and KLF4. Reprod Biomed Online. 2016;32:434–45.CrossRefPubMed
25.
go back to reference Xiao P, Liu W, Zhou H. miR-200b inhibits migration and invasion in non-small cell lung cancer cells via targeting FSCN1. Mol Med Rep. 2016;14:1835–40.PubMed Xiao P, Liu W, Zhou H. miR-200b inhibits migration and invasion in non-small cell lung cancer cells via targeting FSCN1. Mol Med Rep. 2016;14:1835–40.PubMed
Metadata
Title
Overexpression of lncRNA HOXA11-AS promotes cell epithelial–mesenchymal transition by repressing miR-200b in non-small cell lung cancer
Authors
Jian-Hui Chen
Li-Yang Zhou
Suo Xu
Yu-Long Zheng
Yu-Feng Wan
Cheng-Ping Hu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-017-0433-7

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