Skip to main content

Advertisement

SpringerLink
Log in

MIR4435-2HG regulates cancer cell behaviors in oral squamous cell carcinoma cell growth by upregulating TGF-β1

  • Original Article
  • Published:
Odontology Aims and scope Submit manuscript

Abstract

MIR4435-2HG has been characterized as an oncogenic lncRNA in several types of cancer, while its role in oral squamous cell carcinoma (OSCC, a major subtype of oral cancer) has not been characterized. We explored the functionality of MIR4435-2HG in OSCC and investigated its interactions with TGF-β1. Blood samples were extracted from OSCC patients (n = 44) and healthy volunteers (n = 38), RT-qPCR, CCK-8, Transwell assays and western blot were performed in this study. The results showed that levels of MIR4435-2HG and TGF-β1 in plasma were upregulated in OSCC. Across OSCC plasma samples, TGF-β1 and MIR4435-2HG were significantly and positively correlated. Overexpression of MIR4435-2HG resulted in upregulated TGF-β1 expression, while exogenous TGF-β1 treatment had no effect on the expression of MIR4435-2HG. Overexpression of MIR4435-2HG and exogenous TGF-β1 treatment led to promoted, while TGF-β inhibitor led to inhibited migration, proliferation and invasion of cancer cells. Moreover, TGF-β inhibitor led to reduced effects of overexpressing MIR4435-2HG. Therefore, MIR4435-2HG regulates the behaviors of OSCC cells by promoting the expression of TGF-β1.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45(4–5):309–16. https://doi.org/10.1016/j.oraloncology.2008.06.002.

    Article  Google Scholar 

  2. Canto MT, Devesa SS. Oral cavity and pharynx cancer incidence rates in the United States, 1975–1998. Oral Oncol. 2002;38(6):610–7.

    Article  Google Scholar 

  3. Sankaranarayanan R, Ramadas K, Thara S, Muwonge R, Thomas G, Anju G, et al. Long term effect of visual screening on oral cancer incidence and mortality in a randomized trial in Kerala. India. Oral Oncol. 2013;49(4):314–21. https://doi.org/10.1016/j.oraloncology.2012.11.004.

    Article  PubMed  Google Scholar 

  4. Noguti J, De Moura CF, De Jesus GP, Da Silva VH, Hossaka TA, Oshima CT, et al. Metastasis from oral cancer: an overview. Cancer Genomics Proteomics. 2012;9(5):329–35.

    PubMed  Google Scholar 

  5. Kumar M, Nanavati R, Modi TG, Dobariya C. Oral cancer: etiology and risk factors: a review. J Cancer Res Ther. 2016;12(2):458–63. https://doi.org/10.4103/0973-1482.186696.

    Article  PubMed  Google Scholar 

  6. Principe DR, Doll JA, Bauer J, Jung B, Munshi HG, Bartholin L, et al. TGF-beta: duality of function between tumor prevention and carcinogenesis. J Natl Cancer Inst. 2014;106(2):djt369. https://doi.org/10.1093/jnci/djt369.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Murakami T, Hiroshima Y, Miyake K, Kiyuna T, Hwang H. Transforming growth factor-beta (TGF-β) inhibitor modulates cancer stroma in a pancreatic cancer orthotopic mouse model. The American Association for Cancer Research Annual Meeting 2017; Washington, DC. Philadelphia. Cancer Res; 2017. p. 5900.

  8. Syed V. TGF-beta signaling in cancer. J Cell Biochem. 2016;117(6):1279–87. https://doi.org/10.1002/jcb.25496.

    Article  PubMed  Google Scholar 

  9. Yuan JH, Yang F, Wang F, Ma JZ, Guo YJ, Tao QF, et al. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014;25(5):666–81. https://doi.org/10.1016/j.ccr.2014.03.010.

    Article  PubMed  Google Scholar 

  10. Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012;9(6):703–19. https://doi.org/10.4161/rna.20481.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Qian H, Chen L, Huang J, Wang X, Ma S, Cui F, et al. The lncRNA MIR4435-2HG promotes lung cancer progression by activating beta-catenin signalling. J Mol Med (Berl). 2018. https://doi.org/10.1007/s00109-018-1654-5.

    Article  Google Scholar 

  12. Ouyang W, Ren L, Liu G, Chi X, Wei H. LncRNA MIR4435-2HG predicts poor prognosis in patients with colorectal cancer. PeerJ. 2019;7:e6683. https://doi.org/10.7717/peerj.6683.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kong Q, Liang C, Jin Y, Pan Y, Tong D, Kong Q, et al. The lncRNA MIR4435-2HG is upregulated in hepatocellular carcinoma and promotes cancer cell proliferation by upregulating miRNA-487a. Cell Mol Biol Lett. 2019;24:26. https://doi.org/10.1186/s11658-019-0148-y.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Gao W, Chan JY, Wong TS. Long non-coding RNA deregulation in tongue squamous cell carcinoma. Biomed Res Int. 2014;2014:405860. https://doi.org/10.1155/2014/405860.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Zhang S, Tian L, Ma P, Sun Q, Zhang K, Wang G, et al. Potential role of differentially expressed lncRNAs in the pathogenesis of oral squamous cell carcinoma. Arch Oral Biol. 2015;60(10):1581–7. https://doi.org/10.1016/j.archoralbio.2015.08.003.

    Article  PubMed  Google Scholar 

  16. Cirillo N, Hassona Y, Celentano A, Lim KP, Manchella S, Parkinson EK, et al. Cancer-associated fibroblasts regulate keratinocyte cell-cell adhesion via TGF-beta-dependent pathways in genotype-specific oral cancer. Carcinogenesis. 2017;38(1):76–85. https://doi.org/10.1093/carcin/bgw113.

    Article  PubMed  Google Scholar 

  17. Nakamura R, Kayamori K, Oue E, Sakamoto K, Harada K, Yamaguchi A. Transforming growth factor-beta synthesized by stromal cells and cancer cells participates in bone resorption induced by oral squamous cell carcinoma. Biochem Biophys Res Commun. 2015;458(4):777–82. https://doi.org/10.1016/j.bbrc.2015.02.013.

    Article  PubMed  Google Scholar 

  18. Cheng CM, Shiah SG, Huang CC, Hsiao JR, Chang JY. Up-regulation of miR-455-5p by the TGF-beta-SMAD signalling axis promotes the proliferation of oral squamous cancer cells by targeting UBE2B. J Pathol. 2016;240(1):38–49. https://doi.org/10.1002/path.4752.

    Article  PubMed  Google Scholar 

  19. Huang W, Cui X, Chen J, Feng Y, Song E, Li J, et al. Long non-coding RNA NKILA inhibits migration and invasion of tongue squamous cell carcinoma cells via suppressing epithelial-mesenchymal transition. Oncotarget. 2016;7(38):62520–322. https://doi.org/10.18632/oncotarget.11528.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Uhl M, Aulwurm S, Wischhusen J, Weiler M, Ma JY, Almirez R, et al. SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res. 2004;64(21):7954–61. https://doi.org/10.1158/0008-5472.CAN-04-1013.

    Article  PubMed  Google Scholar 

  21. Mohammad KS, Javelaud D, Fournier PG, Niewolna M, McKenna CR, Peng XH, et al. TGF-beta-RI kinase inhibitor SD-208 reduces the development and progression of melanoma bone metastases. Cancer Res. 2011;71(1):175–84. https://doi.org/10.1158/0008-5472.CAN-10-2651.

    Article  PubMed  Google Scholar 

  22. Chen J, Deng Y, Ao L, Song Y, Xu Y, Wang CC, et al. The high-risk HPV oncogene E7 upregulates miR-182 expression through the TGF-beta/Smad pathway in cervical cancer. Cancer Lett. 2019;460:75–85. https://doi.org/10.1016/j.canlet.2019.06.015.

    Article  PubMed  Google Scholar 

Download references

Funding

No funding was received.

Author information

Author notes

  1. Huan Shen and Bin Sun contributed equally to this work.

Authors and Affiliations

  1. Department of Stomatology, PLA Rocket Force General Hospital, Beijing, 100088, People’s Republic of China

    Huan Shen, Bin Sun, Yongjin Yang, Xingwei Cai, Lixia Bi & Lin Deng

  2. School of Basic Medical Sciences, The Fourth Military Medical University, No. 147, West of Changle Road, Xincheng District, Xi’an, 710032, Shannxi, People’s Republic of China

    Luyue Zhang

Authors
  1. Huan Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bin Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yongjin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xingwei Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lixia Bi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lin Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Luyue Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HS and BS: experiments work, data analysis and writing the manuscript. YY, XC, LB and LD: lab work, clinical research and manuscript preparation. LZ: research design, manuscript review and clinical research. Final manuscript has been approved by all authors.

Corresponding author

Correspondence to Luyue Zhang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study passed the review of Ethics Committee of PLA Rocket Force General Hospital. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shen, H., Sun, B., Yang, Y. et al. MIR4435-2HG regulates cancer cell behaviors in oral squamous cell carcinoma cell growth by upregulating TGF-β1. Odontology 108, 553–559 (2020). https://doi.org/10.1007/s10266-020-00488-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10266-020-00488-x

Keywords

Search

Navigation