Skip to main content

Advertisement

Log in

MicroRNA-199-3p targets Sp1 transcription factor to regulate proliferation and epithelial to mesenchymal transition of human lung cancer cells

  • Original Article
  • Published:
3 Biotech Aims and scope Submit manuscript

Abstract

The present study was undertaken to study the function of miRNA-199-3p in the regulation of human lung cancer growth and metastasis. The results showed significant (P < 0.05) downregulation of miRNA-199-3p in lung cancer tissues and cell lines. Overexpression of miR-197 caused considerable inhibition of the viability and colony formation of the lung cancer cells. The inhibition of proliferation was found to be due to the arrest of the SK-LU-1 lung cancer cells. At the G2/M phase of the cell cycle. In silico analysis and subsequent the dual-luciferase assays showed that miR-199-3p targets Sp1 at molecular. The expression of Sp1 was significantly (P < 0.05) upregulated in lung cancer cells and tissues. Nonetheless, miR-199-3p overexpression could cause post-transcriptional suppression of Sp1. Silencing of Sp1suppress the proliferation of SK-LU-1 lung cancer cells. However, overexpression Sp1 transcription factor prevents the tumor-suppressive effects of miR-199-3p on lung cancer cells. Additionally, miR-199-3p was found to suppresses the migration, invasion and epithelial-to-mesenchymal transition of human lung cancer cells. Summing up, miRNA-199-3p/SP1 axis controls the growth and metastasis of SK-LU-1 lung cancer cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig.4

Similar content being viewed by others

References

  • Akhtar N, Bansal JG (2017) Risk factors of lung cancer in nonsmoker. Curr Probl Cancer 41:328–339

    Article  PubMed  Google Scholar 

  • Beishline K, Azizkhan-Clifford J (2015) Sp1 and the ‘hallmarks of cancer.’ FEBS J 282:224–258

    Article  CAS  PubMed  Google Scholar 

  • Bradley CJ, Yabroff KR, Mariotto AB, Zeruto C, Tran Q, Warren JL (2017) Antineoplastic treatment of advanced-stage non-small-cell lung cancer: treatment, survival, and spending (2000 to 2011). J Clin Oncol 35:529–535

    Article  PubMed  PubMed Central  Google Scholar 

  • Castro D, Moreira M, Gouveia AM, Pozza DH, De Mello RA (2017) MicroRNAs in lung cancer. Oncotarget 8:81679

    Article  PubMed  PubMed Central  Google Scholar 

  • Deng YR, Chen XJ, Chen W, Wu LF, Jiang HP, Lin D, Wang LJ, Wang W, Guo SQ (2019) Sp1 contributes to radioresistance of cervical cancer through targeting G2/M cell cycle checkpoint CDK1. Cancer Manag Res 11:5835–5844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DeSantis CE, Miller KD, Dale W, Mohile SG, Cohen HJ, Leach CR, Sauer AG, Jemal A, Siegel RL (2019) Cancer statistics for adults aged 85 years and older, 2019. CA Cancer J Clin 69:452–467

    Article  PubMed  Google Scholar 

  • Fernández-Hernando C, Ramírez CM, Goedeke L, Suárez Y (2013) MicroRNAs in metabolic disease. Arterioscler Thromb Vasc Biol 33:178–185

    Article  PubMed  PubMed Central  Google Scholar 

  • Giovannini C, Fornari F, Dallo R, Gagliardi M, Nipoti E, Vasuri F, Coadă CA, Ravaioli M, Bolondi L, Gramantieri L (2018) MiR-199-3p replacement affects E-cadherin expression through Notch1 targeting in hepatocellular carcinoma. Acta Histochem 120(2):95–102

    Article  CAS  PubMed  Google Scholar 

  • Hosoi Y, Watanabe T, Nakagawa K, Matsumoto Y, Enomoto A, Morita A, Nagawa H, Suzuki N (2004) Upregulation of DNA-dependent protein kinase activity and Sp1 in colorectal cancer. Int Oncol 25:461–468

    CAS  Google Scholar 

  • Hsu PP, Shaw AT (2017) Lung cancer: a wily genetic opponent. Cell 169:777–779

    Article  CAS  PubMed  Google Scholar 

  • Hsu TI, Wang MC, Chen SY, Yeh YM, Su WC, Chang WC, Hung JJ (2012) Sp1 expression regulates lung tumor progression. Oncogene 31:3973–3988

    Article  CAS  PubMed  Google Scholar 

  • Kaidonis G, Pan P, Sarin S, Zheng S, Hwang DG, Chan MF (2020) miR-199-3p is hypermethylated and downregulated in FECD endothelial cells: exploring the miR-199-3p-SP1-DNMT3A methylation axis and its impact on ECM production. Invest Ophthalmol vis Sci 61:1468

    Google Scholar 

  • Koshizuka K, Hanazawa T, Kikkawa N, Arai T, Okato A, Kurozumi A, Kato M, Katada K, Okamoto Y, Seki N (2017) Regulation of ITGA 3 by the anti-tumor miR-199 family inhibits cancer cell migration and invasion in head and neck cancer. Cancer Sci 108:1681–1692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Larsen JE, Nathan V, Osborne JK, Farrow RK, Deb D, Sullivan JP, Dospoy PD, Augustyn A, Hight SK, Sato M, Girard L (2016) ZEB1 drives epithelial-to-mesenchymal transition in lung cancer. J Clin Invest 126:3219–3235

    Article  PubMed  PubMed Central  Google Scholar 

  • Di Leva G, Garofalo M, Croce CM (2014) MicroRNAs in cancer. Annu Rev Pathol 9:287–314

    Article  PubMed  Google Scholar 

  • Liu Y, Du Y, Hu X, Zhao L, Xia W (2018) Upregulation of ceRNA TINCR by SP1 contributes to tumorigenesis in breast cancer. BMC Cancer 18:1–11

    Article  Google Scholar 

  • Mendell JT (2005) MicroRNAs: critical regulators of development, cellular physiology and malignancy. Cell Cycle 4:1179–1184

    Article  CAS  PubMed  Google Scholar 

  • Mihailescu R (2015) Gene expression regulation: lessons from noncoding RNAs. RNA 21:695–696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, Jemal A, Kramer JL, Siegel RL (2019) Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin 69:363–385

    Article  Google Scholar 

  • Oliveto S, Mancino M, Manfrini N, Biffo S (2017) Role of microRNAs in translation regulation and cancer. World J Biol Chem 8:45–56

    Article  PubMed  PubMed Central  Google Scholar 

  • Quintanal-Villalonga Á, Molina-Pinelo S (2019) Epigenetics of lung cancer: a translational perspective. Cellular Oncol 8:1–8

    Google Scholar 

  • Salehi M, Sharifi M (2018) Exosomal miRNAs as novel cancer biomarkers: challenges and opportunities. J Cell Physiol 233:6370–6380

    Article  CAS  PubMed  Google Scholar 

  • Su WZ, Ren LF (2019) MiRNA-199 inhibits malignant progression of lung cancer through mediating RGS17. Eur Rev Med Pharmacol Sci 23:3390–3400

    PubMed  Google Scholar 

  • Suresh R, Ali S, Ahmad A, Philip PA, Sarkar FH (2016) The role of cancer stem cells in recurrent and drug-resistant lung cancer. Lung cancer and personalized medicine: novel therapies and clinical management. Springer, Cham, pp 57–74

    Chapter  Google Scholar 

  • Tan W, Liu B, Qu S, Liang G, Luo W, Gong C (2018) MicroRNAs and cancer: key paradigms in molecular therapy. Oncology Lett 15:2735–2742

    Google Scholar 

  • Tao G, Martin JF (2013) Genetics: microRNAs get to the heart of development. Elife 2:e01710

    Article  PubMed  PubMed Central  Google Scholar 

  • Vannini I, Fanini F, Fabbri M (2018) Emerging roles of microRNAs in cancer. Curr Opin Genet Dev 48:128–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vizcaíno C, Mansilla S, Portugal J (2015) Sp1 transcription factor: a long-standing target in cancer chemotherapy. Pharmacol Ther 152:111–124

    Article  PubMed  Google Scholar 

  • Wang W, Kwon EJ, Tsai LH (2013) MicroRNAs in learning, memory, and neurological diseases. Learn Mem 19:359–368

    Article  Google Scholar 

  • Wang Z, Ma X, Cai Q, Wang X, Yu B, Cai Q, Zhu Z, Li C (2014) MiR-199a-3p promotes gastric cancer progression by targeting ZHX1. FEBS Lett 588:4504–4512

    Article  CAS  PubMed  Google Scholar 

  • Wu KL, Tsai YM, Lien CT, Kuo PL, Hung JY (2019) The roles of microRNA in lung cancer. Int J Mol Sci 20:1611

    Article  CAS  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization: JF and LH; methodology: JF, TL, XJ, BX and LH; formal analysis and investigation: JF and TL; writing—original draft preparation: JF and LH; writing—review and editing critically for important intellectual content: LH; supervision: LH.

Corresponding author

Correspondence to Lijuan Hu.

Ethics declarations

Conflict of interest

All the authors declare that there is no conflict of interest.

Ethical approval

Informed consent was sought from the patients before inclusion in the present study. The research ethics committee of Zhongshan Hospital, Fudan University, Shanghai, China. Approved the study with approval number ZHF0172/2020.

Additional information

Jiajia Fu and Tong Li contributed to this work equally.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fu, J., Li, T., Jiang, X. et al. MicroRNA-199-3p targets Sp1 transcription factor to regulate proliferation and epithelial to mesenchymal transition of human lung cancer cells. 3 Biotech 11, 352 (2021). https://doi.org/10.1007/s13205-021-02881-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13205-021-02881-x

Keywords

Navigation