Open Access

Upregulated microRNA‑671‑3p promotes tumor progression by suppressing forkhead box P2 expression in non‑small‑cell lung cancer

  • Authors:
    • Zhi‑Ying Li
    • Zi‑Zhou Zhang
    • Hui Bi
    • Qiu‑Di Zhang
    • Su‑Juan Zhang
    • Lin Zhou
    • Xiao‑Qin Zhu
    • Jun Zhou
  • View Affiliations

  • Published online on: August 6, 2019     https://doi.org/10.3892/mmr.2019.10563
  • Pages: 3149-3159
  • Copyright: © Li 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

In the present study, the expression of microRNA (miR)‑671‑3p in non‑small‑cell lung cancer (NSCLC) was detected via reverse transcription‑quantitative polymerase chain reaction analysis, and its role in cell proliferation, apoptosis, migration and invasion was investigated via Cell Counting Kit‑8, colony formation, flow cytometry, Transwell and scratch assays, respectively. It was observed that the expression of miR‑671‑3p was upregulated in NSCLC tissues and cell lines (A549 and H1975). Treatment with miR‑671‑3p inhibitors suppressed cell proliferation, migration and invasion, and increased apoptosis in vitro, suggesting that miR‑671‑3p functions as an oncogene in NSCLC. In addition, forkhead box P2 (FOXP2) has been reported to be a tumor suppressor that is downregulated in several types of cancer, and its low expression was confirmed in NSCLC tissues and cell lines in the current study via western blotting. The results of the luciferase reporter assay also demonstrated that miR‑671‑3p targeted directly the 3'‑untranslated region of FOXP2. Furthermore, overexpression of FOXP2 in A549 and H1975 cell lines suppressed the growth, migration and invasion, and promoted apoptosis, whereas these effects were reversed by transfection with miR‑671‑3p mimics, suggesting that miR‑671‑3p promoted tumor progression via regulating FOXP2. Taken together, the results reported in the present study implied that miR‑671‑3p may be a potential therapeutic target in NSCLC.

References

1 

Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Zhang Y, Yang Q and Wang S: MicroRNAs: A new key in lung cancer. Cancer Chemother Pharmacol. 74:1105–1111. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Yin R, Guo L, Zhang W and Zheng J: The pleiotropic effects of mirnas on tumor angiogenesis. J Cell Biochem. 116:1807–1815. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Ma L, Teruya-Feldstein J and Weinberg RA: Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 449:682–688. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Hess KR, Varadhachary GR, Taylor SH, Wei W, Raber MN, Lenzi R and Abbruzzese JL: Metastatic patterns in adenocarcinoma. Cancer. 106:1624–1633. 2006. View Article : Google Scholar : PubMed/NCBI

7 

McIntyre A and Ganti AK: Lung cancer-A global perspective. J Surg Oncol. 115:550–554. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Cho WC: Role of miRNAs in lung cancer. Expert Rev Mol Diagn. 9:773–776. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Hashemi ZS, Khalili S, Forouzandeh Moghadam M and Sadroddiny E: Lung cancer and miRNAs: A possible remedy for anti-metastatic, therapeutic and diagnostic applications. Expert Rev Respir Med. 11:147–157. 2017. View Article : Google Scholar : PubMed/NCBI

10 

Rusek AM, Abba M, Eljaszewicz A, Moniuszko M, Niklinski J and Allgayer H: MicroRNA modulators of epigenetic regulation, the tumor microenvironment and the immune system in lung cancer. Mol Cancer. 14:342015. View Article : Google Scholar : PubMed/NCBI

11 

Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, Wilson M, Wang X, Shelton J, Shingara J, et al: The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 67:7713–7722. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Ntoumou E, Tzetis M, Braoudaki M, Lambrou G, Poulou M, Malizos K, Stefanou N, Anastasopoulou L and Tsezou A: Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes. Clin Epigenetics. 9:1272017. View Article : Google Scholar : PubMed/NCBI

13 

Xiong DD, Chen H, He RQ, Lan AH, Zhong JC, Chen G, Feng ZB and Wei KL: MicroRNA-671-3p inhibits the development of breast cancer: A study based on in vitro experiments, in-house quantitative polymerase chain reaction and bioinformatics analysis. Int J Oncol. 52:1801–1814. 2018.PubMed/NCBI

14 

Chen MT, Sun HF, Li LD, Zhao Y, Yang LP, Gao SP and Jin W: Downregulation of FOXP2 promotes breast cancer migration and invasion through TGFβ/SMAD signaling pathway. Oncol Lett. 15:8582–8588. 2018.PubMed/NCBI

15 

Jia WZ, Yu T, An Q, Yang H, Zhang Z, Liu X and Xiao G: MicroRNA-190 regulates FOXP2 genes in human gastric cancer. Onco Targets Ther. 9:3643–3651. 2016.PubMed/NCBI

16 

Cuiffo BG, Campagne A, Bell GW, Lembo A, Orso F, Lien EC, Bhasin MK, Raimo M, Hanson SE, Marusyk A, et al: MSC-regulated microRNAs converge on the transcription factor FOXP2 and promote breast cancer metastasis. Cell Stem Cell. 15:762–774. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Yu Z, Lin X, Tian M and Chang W: microRNA-196b promotes cell migration and invasion by targeting FOXP2 in hepatocellular carcinoma. Oncol Rep. 39:731–738. 2018.PubMed/NCBI

18 

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

19 

Chen X, Lu P, Wang DD, Yang SJ, Wu Y, Shen HY, Zhong SL, Zhao JH and Tang JH: The role of miRNAs in drug resistance and prognosis of breast cancer formalin-fixed paraffin-embedded tissues. Gene. 595:221–226. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Jiménez MJ, Balbin M, Alvarez J, Komori T, Bianco P, Holmbeck K, Birkedal-Hansen H, López JM and López-Otín C: A regulatory cascade involving retinoic acid, Cbfa1, and matrix metalloproteinases is coupled to the development of a process of perichondrial invasion and osteogenic differentiation during bone formation. J Cell Biol. 155:1333–1344. 2001. View Article : Google Scholar : PubMed/NCBI

22 

Khokha R and Denhardt DT: Matrix metalloproteinases and tissue inhibitor of metalloproteinases: A review of their role in tumorigenesis and tissue invasion. Invasion Metastasis. 9:391–405. 1989.PubMed/NCBI

23 

Tan W, Liu B, Qu S, Liang G, Luo W and Gong C: MicroRNAs and cancer: Key paradigms in molecular therapy. Oncol Lett. 15:2735–2742. 2018.PubMed/NCBI

24 

Yang Y, Ding L, Hu Q, Xia J, Sun J, Wang X, Xiong H, Gurbani D, Li L, Liu Y and Liu A: MicroRNA-218 functions as a tumor suppressor in lung cancer by targeting IL-6/STAT3 and negatively correlates with poor prognosis. Mol Cancer. 16:1412017. View Article : Google Scholar : PubMed/NCBI

25 

Yang Y, Li H, Liu Y, Chi C, Ni J and Lin X: miR-4319 hinders YAP expression to restrain non-small cell lung cancer growth through regulation of LIN28-mediated RFX5 stability. Biomed Pharmacother. 115:1089562019. View Article : Google Scholar : PubMed/NCBI

26 

Tan X, Fu Y, Chen L, Lee W, Lai Y Rezaei K, Tabbara S, Latham P, Teal CB, Man YG, et al: miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer. Oncotarget. 7:293–307. 2016.PubMed/NCBI

27 

Chiu YC, Li MY, Liu YH, Ding JY, Yu JY and Wang TW: Foxp2 regulates neuronal differentiation and neuronal subtype specification. Dev Neurobiol. 74:723–738. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Katoh M and Katoh M: Human FOX gene family (Review). Int J Oncol. 25:1495–1500. 2004.PubMed/NCBI

29 

Tsui D, Vessey JP, Tomita H, Kaplan DR and Miller FD: FoxP2 regulates neurogenesis during embryonic cortical development. J Neurosci. 33:244–258. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Enard W, Przeworski M, Fisher SE, Lai CS, Wiebe V, Kitano T, Monaco AP and Pääbo S: Molecular evolution of FOXP2, a gene involved in speech and language. Nature. 418:869–872. 2002. View Article : Google Scholar : PubMed/NCBI

31 

Herrero MJ and Gitton Y: The untold stories of the speech gene, the FOXP2 cancer gene. Genes Cancer. 9:11–38. 2018.PubMed/NCBI

32 

Campbell AJ, Lyne L, Brown PJ, Launchbury RJ, Bignone P, Chi J, Roncador G, Lawrie CH, Gatter KC, Kusec R and Banham AH: Aberrant expression of the neuronal transcription factor FOXP2 in neoplastic plasma cells. Br J Haematol. 149:221–230. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Yan X, Zhou H and Zhang T, Xu P, Zhang S, Huang W, Yang L, Gu X, Ni R and Zhang T: Downregulation of FOXP2 promoter human hepatocellular carcinoma cell invasion. Tumour Biol. 36:9611–9619. 2015. View Article : Google Scholar : PubMed/NCBI

34 

Song XL, Tang Y, Lei XH, Zhao SC and Wu ZQ: miR-618 inhibits prostate cancer migration and invasion by targeting FOXP2. J Cancer. 8:2501–2510. 2017. View Article : Google Scholar : PubMed/NCBI

35 

Chen MT, Sun HF, Li LD, Zhao Y, Yang LP, Gao SP and Jin W: Downregulation of FOXP2 promotes breast cancer migration and invasion through TGFβ/SMAD signaling pathway. Oncol Lett. 15:8582–8588. 2018.PubMed/NCBI

36 

Cuiffo BG and Karnoub AE: Silencing FOXP2 in breast cancer cells promotes cancer stem cell traits and metastasis. Mol Cell Oncol. 3:e10190222015. View Article : Google Scholar : PubMed/NCBI

37 

Wu J, Liu P, Tang H, Shuang Z, Qiu Q, Zhang L, Song C, Liu L, Xie X and Xiao X: FOXP2 Promotes tumor proliferation and metastasis by targeting GRP78 in triple-negative breast cancer. Curr Cancer Drug Targets. 18:382–389. 2018. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

October 2019
Volume 20 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Li, Z., Zhang, Z., Bi, H., Zhang, Q., Zhang, S., Zhou, L. ... Zhou, J. (2019). Upregulated microRNA‑671‑3p promotes tumor progression by suppressing forkhead box P2 expression in non‑small‑cell lung cancer. Molecular Medicine Reports, 20, 3149-3159. https://doi.org/10.3892/mmr.2019.10563
MLA
Li, Z., Zhang, Z., Bi, H., Zhang, Q., Zhang, S., Zhou, L., Zhu, X., Zhou, J."Upregulated microRNA‑671‑3p promotes tumor progression by suppressing forkhead box P2 expression in non‑small‑cell lung cancer". Molecular Medicine Reports 20.4 (2019): 3149-3159.
Chicago
Li, Z., Zhang, Z., Bi, H., Zhang, Q., Zhang, S., Zhou, L., Zhu, X., Zhou, J."Upregulated microRNA‑671‑3p promotes tumor progression by suppressing forkhead box P2 expression in non‑small‑cell lung cancer". Molecular Medicine Reports 20, no. 4 (2019): 3149-3159. https://doi.org/10.3892/mmr.2019.10563