Open Access

Long non‑coding RNA‑neighboring enhancer of FOXA2 inhibits the migration and invasion of small cell lung carcinoma cells by downregulating transforming growth factor‑β1

  • Authors:
    • Lei Wu
    • Pan Wang
  • View Affiliations

  • Published online on: March 15, 2019     https://doi.org/10.3892/ol.2019.10152
  • Pages: 4969-4975
  • Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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


Abstract

Long non‑coding RNA‑neighboring enhancer of FOXA2 (lncRNA‑NEF) is a recently identified tumor suppressor in hepatocellular carcinoma. The present study aimed to investigate the role of lncRNA‑NEF in small cell lung carcinoma (SCLC). Expression levels of lncRNA‑NEF in the lung biopsy tissues and plasma samples from patients with SCLC and from healthy controls were detected using reverse transcription‑quantitative polymerase chain reaction. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic value of lncRNA‑NEF as a marker of SCLC. The association between plasma levels of lncRNA‑NEF and the clinical data of patients was analyzed using the χ2 test. An lncRNA‑NEF expression vector was prepared and transfected into SCLC cells, and cellular migration and invasion were detected using Transwell migration and invasion assays, respectively. The expression of transforming growth factor β1 (TGF‑β1) was detected using western blotting. The results demonstrated that the expression level of lncRNA‑NEF was lower in patients with SCLC compared with that in healthy controls. The expression level of lncRNA‑NEF in the plasma was associated with distant tumor metastasis. lncRNA‑NEF overexpression inhibited SCLC cell migration and invasion, resulting in TGF‑β1 downregulation, while treatment with exogenous TGF‑β1 reduced the inhibitory effects of lncRNA‑NEF overexpression on migration and invasion. Therefore, it was concluded that lncRNA‑NEF inhibited the migration and invasion of SCLC cells, which was potentially associated with the downregulation of TGF‑β1.

References

1 

Heerboth S, Housman G, Leary M, Longacre M, Byler S, Lapinska K, Willbanks A and Sarkar S: EMT and tumor metastasis. Clin Transl Med. 4:62015. View Article : Google Scholar : PubMed/NCBI

2 

Ghajar CM: Metastasis prevention by targeting the dormant niche. Nat Rev Cancer. 15:238–247. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Ettinger DS, Akerley W, Bepler G, Blum MG, Chang A, Cheney RT, Chirieac LR, D'Amico TA, Demmy TL, Ganti AK, et al: Non-small cell lung cancer. J Natl Compr Canc Netw. 8:740–801. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Tanoue LT, Tanner NT, Gould MK and Silvestri GA: Lung cancer screening. Am J Respir Crit Care Med. 191:19–33. 2015. View Article : Google Scholar : PubMed/NCBI

6 

David CJ, Huang YH, Chen M, Su J, Zou Y, Bardeesy N, Iacobuzio-Donahue CA and Massagué J: TGF-β tumor suppression through a lethal EMT. Cell. 164:1015–1030. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Yu JR, Tai Y, Jin Y, Hammell MC, Wilkinson JE, Roe JS, Vakoc CR and Van Aelst L: TGF-β/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis. Genes Dev. 29:250–261. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Yang H, Wang L, Zhao J, Chen Y, Lei Z, Liu X, Xia W, Guo L and Zhang HT: TGF-β-activated SMAD3/4 complex transcriptionally upregulates N-cadherin expression in non-small cell lung cancer. Lung Cancer. 87:249–257. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Li C, Wan L, Liu Z, Xu G, Wang S, Su Z, Zhang Y, Zhang C, Liu X, Lei Z and Zhang HT: Long non-coding RNA XIST promotes TGF-β-induced epithelial-mesenchymal transition by regulating miR-367/141-ZEB2 axis in non-small-cell lung cancer. Cancer Lett. 418:185–195. 2018. View Article : Google Scholar : PubMed/NCBI

10 

Fatica A and Bozzoni I: Long non-coding RNAs: New players in cell differentiation and development. Nat Rev Genet. 15:7–21. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Liang WC, Ren JL, Wong CW, Chan SO, Waye MM, Fu WM and Zhang JF: LncRNA-NEF antagonized epithelial to mesenchymal transition and cancer metastasis via cis-regulating FOXA2 and inactivating Wnt/β-catenin signaling. Oncogene. 37:1445–1456. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Rami-Porta R, Asamura H, Travis WD and Rusch VW: Lung cancer-major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 67:138–155. 2017. View Article : Google Scholar : PubMed/NCBI

13 

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

14 

Peng Z, Zhang C and Duan C: Functions and mechanisms of long noncoding RNAs in lung cancer. Onco Targets Ther. 9:4411–4424. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Niu Y, Ma F, Huang W, Fang S, Li M, Wei T and Guo L: Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2. Mol Cancer. 16:52017. View Article : Google Scholar : PubMed/NCBI

16 

Zeng L, Yang R, Wang J and Liu Y: The relationship between the expression of LncRNA EXOC7 and the prognosis of patients with small cell lung cancer. Tumor. 37:269–274. 2017.

17 

Wan L, Zhang L, Fan K and Wang JJ: Diagnostic significance of circulating long noncoding RNA PCAT6 in patients with non-small cell lung cancer. Onco Targets Ther. 10:5695–5702. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Wang HM, Lu JH, Chen WY and Gu AQ: Upregulated lncRNA-UCA1 contributes to progression of lung cancer and is closely related to clinical diagnosis as a predictive biomarker in plasma. Int J Clin Exp Med. 8:11824–11830. 2015.PubMed/NCBI

19 

Akhurst RJ and Derynck R: TGF-beta signaling in cancer-a double-edged sword. Trends Cell Biol. 11:S44–S51. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Seoane J and Gomis RR: TGF-β family signaling in tumor suppression and cancer progression. Cold Spring Harb Perspect Biol. 9(pii): a0222772017. View Article : Google Scholar : PubMed/NCBI

21 

Wang L, Yang H, Lei Z, Zhao J, Chen Y, Chen P, Li C, Zeng Y, Liu Z, Liu X and Zhang HT: Repression of TIF1γ by SOX2 promotes TGF-β-induced epithelial-mesenchymal transition in non-small-cell lung cancer. Oncogene. 35:867–877. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Zhang D, Qin H, Leng Y, Li X, Zhang L, Bai D, Meng Y and Wang J: LncRNA MEG3 overexpression inhibits the development of diabetic retinopathy by regulating TGF-β1 and VEGF. Exp Ther Med. 16:2337–2342. 2018.PubMed/NCBI

23 

Zhao B, Lu YL, Yang Y, Hu LB, Bai Y, Li RQ, Zhang GY, Li J, Bi CW, Yang LB, et al: Overexpression of lncRNA ANRIL promoted the proliferation and migration of prostate cancer cells via regulating let-7a/TGF-β1/Smad signaling pathway. Cancer Biomark. 21:613–620. 2018. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

June 2019
Volume 17 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Wu, L., & Wu, L. (2019). Long non‑coding RNA‑neighboring enhancer of FOXA2 inhibits the migration and invasion of small cell lung carcinoma cells by downregulating transforming growth factor‑β1. Oncology Letters, 17, 4969-4975. https://doi.org/10.3892/ol.2019.10152
MLA
Wu, L., Wang, P."Long non‑coding RNA‑neighboring enhancer of FOXA2 inhibits the migration and invasion of small cell lung carcinoma cells by downregulating transforming growth factor‑β1". Oncology Letters 17.6 (2019): 4969-4975.
Chicago
Wu, L., Wang, P."Long non‑coding RNA‑neighboring enhancer of FOXA2 inhibits the migration and invasion of small cell lung carcinoma cells by downregulating transforming growth factor‑β1". Oncology Letters 17, no. 6 (2019): 4969-4975. https://doi.org/10.3892/ol.2019.10152