LncRNA AWPPH participates in the metastasis of non‑small cell lung cancer by upregulating TGF‑β1 expression

Huo,Yanxia; Li,Aimin; Wang,Zhihua

doi:10.3892/ol.2019.10754

LncRNA AWPPH participates in the metastasis of non‑small cell lung cancer by upregulating TGF‑β1 expression

Authors:
- Yanxia Huo
- Aimin Li
- Zhihua Wang
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Affiliations: Department of Respiratory Medicine, Affiliated Xing Tai People Hospital of Hebei Medical University, Xingtai, Hebei 054031, P.R. China
Published online on: August 16, 2019 https://doi.org/10.3892/ol.2019.10754
Pages: 4246-4252
Copyright: © Huo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNA (lncRNA) AWPPH is a characterized oncogenic lncRNA in hepatocellular carcinoma and bladder cancer. The aim of the present study was to investigate the potential involvement of AWPPH in non‑small cell lung cancer (NSCLC). Expression of AWPPH in lung biopsy tissues and serum of both healthy controls and patients with NSCLC with different tumor sizes, and with and without distant tumor metastasis was detected by reverse transcription‑quantitative PCR. AWPPH expression vector was constructed and transfected into cells of human NSCLC cell lines. Expression of TGF‑β1 was detected by western blot analysis. Cell migration and invasion were detected by Transwell migration and invasion assay. It was observed that AWPPH was significantly upregulated in patients with NSCLC, while AWPPH expression level did not increase with the increase of tumor size. In contrast, AWPPH expression levels were significantly higher in patients with distant metastasis than in patients without tumor distant metastasis. AWPPH overexpression promoted TGF‑β1 expression in NSCLC cells, while TGF‑β1 treatment showed no significant effects on AWPPH expression. AWPPH overexpression promoted NSCLC cell migration and invasion, while TGF‑β signaling inhibition reduced this enhancing effect. Therefore, AWPPH may promote the metastasis, but not the growth of NSCLC by upregulating TGF‑β1 expression.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Gridelli C, Rossi A, Carbone DP, Guarize J, Karachaliou N, Mok T, Petrella F, Spaggiari L and Rosell R: Non-small-cell lung cancer. Nat Rev Dis Primers. 1:150092015. View Article : Google Scholar : PubMed/NCBI
3	Yeo CD and Joo H: P1.01–011 Roflumilast Attenuates Benzo(a)Pyrene-Induced Lung Cancer via Suppression of Airway Inflammation in Murine Model. J Thorac Oncol. 12 (Suppl):S4542017. View Article : Google Scholar
4	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
5	Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, Dahlin CM, Blinderman CD, Jacobsen J, Pirl WF, et al: Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 363:733–742. 2010. View Article : Google Scholar : PubMed/NCBI
6	Cao M, Seike M, Soeno C, Mizutani H, Kitamura K, Minegishi Y, Noro R, Yoshimura A, Cai L and Gemma A: MiR-23a regulates TGF-β-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells. Int J Oncol. 41:869–875. 2012. View Article : Google Scholar : PubMed/NCBI
7	Zhang J, Wang J, Zhao F, Liu Q, Jiang K and Yang GH: MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). Clin Chim Acta. 411:846–852. 2010. View Article : Google Scholar : PubMed/NCBI
8	Xiao D and He J: Epithelial mesenchymal transition and lung cancer. J Thorac Dis. 2:154–159. 2010.PubMed/NCBI
9	Gutschner T and Diederichs S: The hallmarks of cancer: A long non-coding RNA point of view. RNA Biol. 9:703–719. 2012. View Article : Google Scholar : PubMed/NCBI
10	Yuan JH, Yang F, Wang F, Ma JZ, Guo YJ, Tao QF, Liu F, Pan W, Wang TT, Zhou CC, et al: A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 25:666–681. 2014. View Article : Google Scholar : PubMed/NCBI
11	Zhao X, Liu Y and Yu S: Long noncoding RNA AWPPH promotes hepatocellular carcinoma progression through YBX1 and serves as a prognostic biomarker. Biochim Biophys Acta Mol Basis Dis. 1863:1805–1816. 2017. View Article : Google Scholar : PubMed/NCBI
12	Zhu F, Zhang X, Yu Q, Han G, Diao F, Wu C and Zhang Y: LncRNA AWPPH inhibits SMAD4 via EZH2 to regulate bladder cancer progression. J Cell Biochem. 119:4496–4505. 2018. View Article : Google Scholar : PubMed/NCBI
13	Wang K, Li X, Song C and Li M: LncRNA AWPPH promotes the growth of triple-negative breast cancer by up-regulating frizzled homolog 7 (FZD7). Biosci Rep. 28(pii): BSR201812232018. View Article : Google Scholar
14	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
15	Scheffler M, Bos M, Gardizi M, König K, Michels S, Fassunke J, Heydt C, Künstlinger H, Ihle M, Ueckeroth F, et al: PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies. Oncotarget. 6:1315–1326. 2015. View Article : Google Scholar : PubMed/NCBI
16	Pikor LA, Ramnarine VR, Lam S and Lam WL: Genetic alterations defining NSCLC subtypes and their therapeutic implications. Lung Cance. 82:179–189. 2013. View Article : Google Scholar
17	Cheng N, Li X, Zhao C, Ren S, Chen X, Cai W, Zhao M, Zhang Y, Li J, Wang Q and Zhou C: Microarray expression profile of long non-coding RNAs in EGFR-TKIs resistance of human non-small cell lung cancer. Oncol Rep. 33:833–839. 2015. View Article : Google Scholar : PubMed/NCBI
18	Yang YR, Zang SZ, Zhong CL, Li YX, Zhao SS and Feng XJ: Increased expression of the lncRNA PVT1 promotes tumorigenesis in non-small cell lung cancer. Int J Clin Exp Pathol. 7:6929–6935. 2014.PubMed/NCBI
19	Lu KH, Li W, Liu XH, Sun M, Zhang ML, Wu WQ, Xie WP and Hou YY: Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer. 13:4612013. View Article : Google Scholar : PubMed/NCBI
20	Katsuno Y, Lamouille S and Derynck R: TGF-β signaling and epithelial-mesenchymal transition in cancer progression. Curr Opin Oncol. 25:76–84. 2013. View Article : Google Scholar : PubMed/NCBI
21	Micalizzi DS, Farabaugh SM and Ford HL: Epithelial-mesenchymal transition in cancer: Parallels between normal development and tumor progression. J Mammary Gland Biol Neoplasia. 15:117–134. 2010. View Article : Google Scholar : PubMed/NCBI