Long non-coding RNA ZEB2-AS1 promotes proliferation and inhibits apoptosis in human lung cancer cells

Guo,Yang; Hu,Ying; Hu,Mingming; He,Jiabei; Li,Baolan

doi:10.3892/ol.2018.7918

Long non-coding RNA ZEB2-AS1 promotes proliferation and inhibits apoptosis in human lung cancer cells

Authors:
- Yang Guo
- Ying Hu
- Mingming Hu
- Jiabei He
- Baolan Li
View Affiliations

Affiliations: General Department Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China
Published online on: February 1, 2018 https://doi.org/10.3892/ol.2018.7918
Pages: 5220-5226

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Lung cancer is among the leading causes of cancer‑associated mortality worldwide, with a low 5‑year survival rate of 16.1%. However, the underlying molecular mechanisms behind lung cancer tumorigenesis remain largely unknown. Long non‑coding RNAs (lncRNAs) have been demonstrated to serve a function in the tumorigenesis of multiple types of cancer. The objective of the present study was to identify the function of a newly identified lncRNA zinc finger E‑box‑binding homeobox 2 antisense RNA 1 (ZEB2‑AS1) in human lung cancer. Results demonstrated that the transcript level of ZEB2‑AS1 in human lung cancer was markedly upregulated in vivo and in vitro. The knockdown of ZEB2‑AS1 in A549 and NCI‑H292 cells, and the overexpression of ZEB2‑AS1 in H‑125 and H1975 cells, altered colony formation and cell proliferative rate, as examined using colony formation and cell proliferation assays. Western blot analysis revealed that the knockdown of ZEB2‑AS1 in A549 and NCI‑H292 cells increased the protein levels of B‑cell lymphoma 2 (Bcl‑2), Bcl-2-associated X protein (Bax), caspase‑3 and ‑9, upregulated the relative activities of caspase‑3 and ‑9, and had no observable effect on caspase‑8 activity. Similarly, the overexpression of ZEB2‑AS1 in H‑125 and H1975 cells resulted in decreased expression of caspase‑3, caspase‑9, Bcl‑2 and Bax. The results identified the effects of lncRNA ZEB2‑AS1 on lung cancer progression through promoting its proliferation and inhibiting cell apoptosis, indicating that ZEB2‑AS1 may serve as a novel prognostic factor for the diagnosis and treatment of human lung cancer in the clinic.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Pikor LA, Ramnarine VR, Lam S and Lam WL: Genetic alterations defining NSCLC subtypes and their therapeutic implications. Lung Cancer. 82:179–189. 2013. View Article : Google Scholar : PubMed/NCBI
3	Youlden DR, Cramb SM and Baade PD: The international epidemiology of lung cancer: Geographical distribution and secular trends. J Thorac Oncol. 3:819–831. 2008. View Article : Google Scholar : PubMed/NCBI
4	Dela Cruz CS, Tanoue LT and Matthay RA: Lung cancer: Epidemiology, etiology, and prevention. Clin Chest Med. 32:605–644. 2011. View Article : Google Scholar : PubMed/NCBI
5	Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, Nishida H, Yap CC, Suzuki M, Kawai J, et al: Antisense transcription in the mammalian transcriptome. Science. 309:1564–1566. 2005. View Article : Google Scholar : PubMed/NCBI
6	Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A and Rinn JL: Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 25:1915–1927. 2011. View Article : Google Scholar : PubMed/NCBI
7	Brown CJ, Ballabio A, Rupert JL, Lafreniere RG, Grompe M, Tonlorenzi R and Willard HF: A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature. 349:38–44. 1991. View Article : Google Scholar : PubMed/NCBI
8	Rinn JL: lncRNAs: Linking RNA to chromatin. Cold Spring Harb Perspect Biol. 6:a0186142014. View Article : Google Scholar : PubMed/NCBI
9	Goff LA and Rinn JL: Linking RNA biology to lncRNAs. Genome Res. 25:1456–1465. 2015. View Article : Google Scholar : PubMed/NCBI
10	Li M, Qiu M, Xu Y, Mao Q, Wang J, Dong G, Xia W, Yin R and Xu L: Differentially expressed protein-coding genes and long noncoding RNA in early-stage lung cancer. Tumour Biol. 36:9969–9978. 2015. View Article : Google Scholar : PubMed/NCBI
11	Yang Y, Li H, Hou S, Hu B, Liu J and Wang J: The noncoding RNA expression profile and the effect of lncRNA AK126698 on cisplatin resistance in non-small-cell lung cancer cell. PLoS One. 8:e653092013. View Article : Google Scholar : PubMed/NCBI
12	Graham TR, Zhau HE, Odero-Marah VA, Osunkoya AO, Kimbro KS, Tighiouart M, Liu T, Simons JW and O'Regan RM: Insulin-like growth factor-I-dependent up-regulation of ZEB1 drives epithelial-to-mesenchymal transition in human prostate cancer cells. Cancer Res. 68:2479–2488. 2008. View Article : Google Scholar : PubMed/NCBI
13	Sanchez-Tilló E, de Barrios O, Siles L, Amendola PG, Darling DS, Cuatrecasas M, Castells A and Postigo A: ZEB1 promotes invasiveness of colorectal carcinoma cells through the opposing regulation of uPA and PAI-1. Clin Cancer Res. 19:1071–1082. 2013. View Article : Google Scholar : PubMed/NCBI
14	Lan T, Chang L, Wu L and Yuan Y: Downregulation of ZEB2-AS1 decreased tumor growth and metastasis in hepatocellular carcinoma. Mol Med Rep. 14:4606–4612. 2016. View Article : Google Scholar : PubMed/NCBI
15	Li T, Xie J, Shen C, Cheng D, Shi Y, Wu Z, Deng X, Chen H, Shen B, Peng C, et al: Upregulation of long noncoding RNA ZEB1-AS1 promotes tumor metastasis and predicts poor prognosis in hepatocellular carcinoma. Oncogene. 35:1575–1584. 2016. View Article : Google Scholar : PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Devesa SS, Bray F, Vizcaino AP and Parkin DM: International lung cancer trends by histologic type: Male: Female differences diminishing and adenocarcinoma rates rising. Int J Cancer. 117:294–299. 2005. View Article : Google Scholar : PubMed/NCBI
18	Zeng H, Zheng R, Guo Y, Zhang S, Zou X, Wang N, Zhang L, Tang J, Chen J, Wei K, et al: Cancer survival in China, 2003–2005: A population-based study. Int J Cancer. 136:1921–1930. 2015. View Article : Google Scholar : PubMed/NCBI
19	Song N, Liu H, Ma X and Zhang S: Placental growth factor promotes ovarian cancer cell invasion via ZEB2. Cell Physiol Biochem. 38:351–358. 2016. View Article : Google Scholar : PubMed/NCBI
20	Yi X, Shi S, Li X and Zhao L: Expression and clinical significance of ZEB2 and E-cadherin in nasopharyngeal carcinoma. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 29:1648–1651. 2015.(In Chinese). PubMed/NCBI
21	Li J, Yuan J, Yuan X, Zhao J, Zhang Z, Weng L and Liu J: MicroRNA-200b inhibits the growth and metastasis of glioma cells via targeting ZEB2. Int J Oncol. 48:541–550. 2016. View Article : Google Scholar : PubMed/NCBI
22	Pang X, Huang K, Zhang Q, Zhang Y and Niu J: miR-154 targeting ZEB2 in hepatocellular carcinoma functions as a potential tumor suppressor. Oncol Rep. 34:3272–3279. 2015. View Article : Google Scholar : PubMed/NCBI
23	Kerr JF, Wyllie AH and Currie AR: Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 26:239–257. 1972. View Article : Google Scholar : PubMed/NCBI
24	Dejean LM, Martinez-Caballero S, Manon S and Kinnally KW: Regulation of the mitochondrial apoptosis-induced channel, MAC, by BCL-2 family proteins. Biochim Biophys Acta. 1762:191–201. 2006. View Article : Google Scholar : PubMed/NCBI
25	Wajant H: The Fas signaling pathway: More than a paradigm. Science. 296:1635–1636. 2002. View Article : Google Scholar : PubMed/NCBI
26	Bejarano I, Espino J, Gonzalez-Flores D, Casado JG, Redondo PC, Rosado JA, Barriga C, Pariente JA and Rodríguez AB: Role of calcium signals on hydrogen peroxide-induced apoptosis in human myeloid HL-60 cells. Int J Biomed Sci. 5:246–256. 2009.PubMed/NCBI
27	Murphy KM, Ranganathan V, Farnsworth ML, Kavallaris M and Lock RB: Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells. Cell Death Differ. 7:102–111. 2000. View Article : Google Scholar : PubMed/NCBI
28	Chen G and Goeddel DV: TNF-R1 signaling: A beautiful pathway. Science. 296:1634–1635. 2002. View Article : Google Scholar : PubMed/NCBI