Skip to main content

Advertisement

SpringerLink
Log in

Knockdown of long non-coding RNA RP11-297P16.3 inhibits the migration and invasion of laryngeal squamous carcinoma cells

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Purpose

Laryngeal cancer has a poor prognosis when progressing to an advanced stage with limited treatment options. Therefore, understanding the underlying mechanisms is important to identify novel treatment targets. Long non-coding RNAs (lncRNAs) have been shown to play oncogenic roles in cancer, including in laryngeal cancer. We previously discovered that the lncRNA RP11-297P16.3 is overexpressed in laryngeal squamous cell carcinoma (LSCC) based on RNA-sequencing data. Therefore, the aim of the present study was to investigate the effects of knockdown of RP11-297P16.3 on the migration and invasion of LSCC cells, and the significance of these effects.

Methods

Six methods were employed to assess the function of RP11-297P16.3 including gene silencing, RT-PCR, the 5-Ethynyl-20-deoxyuridine (EdU) staining assay, Scratch wound-healing assay, transwell assay, and Western blot.

Results

The results show that the expression of RP11-297P16.3 in the si-lncRNA group was significantly decreased compared with those in the BC (blank control) and NC (negative control) groups. Moreover, knockdown of RP11-297P16.3 significantly inhibited the migration and invasion of LSCC cells but had no effect on cell proliferation. The protein expression of N-cadherin and vimentin was notably decreased after RP11-297P16.3 knockdown; whereas, the protein expression of cadherin was significantly increased

Conclusion

These results suggested that RP11-297P16.3 may inhibit the migration and invasion of LSCC cells by regulating the epithelial–mesenchymal transition process, suggesting that RP11-297P16.3 is a potential new target for treating LSCC.

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
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  Google Scholar 

  2. Hamilton DW, Bins JE, McMeekin P, Pedersen A, Steen N, De Soyza A, et al. Quality compared to quantity of life in laryngeal cancer: a time trade-off study. Head Neck. 2016;38(S1):E631-637.

    Article  Google Scholar 

  3. Tamaki A, Miles BA, Lango M, Kowalski L, Zender CA. AHNS series. Do you know your guidelines? Review of current knowledge on laryngeal cancer. Head Neck. 2018;40(1):170–81.

    Article  Google Scholar 

  4. Obid R, Redlich M, Tomeh C. The treatment of laryngeal cancer. Oral Maxillofac Surg Clin North Am. 2019;31(1):1–11.

    Article  Google Scholar 

  5. Dudas J, Ladanyi A, Ingruber J, Steinbichler TB, Riechelmann H. Epithelial to mesenchymal transition. A mechanism that fuels cancer radio/chemoresistance. Cells. 2020;9(2):428.

    Article  CAS  Google Scholar 

  6. Brabletz T, Kalluri R, Nieto MA, Weinberg RA. EMT in cancer. Nat Rev Cancer. 2018;18(2):128–34.

    Article  CAS  Google Scholar 

  7. Goodall GJ, Wickramasinghe VO. RNA in cancer. Nat Rev Cancer. 2021;21(1):22–36.

    Article  CAS  Google Scholar 

  8. Grixti JM, Ayers D. Long noncoding RNAs and their link to cancer. Noncoding RNA Res. 2020;5(2):77–82.

    Article  CAS  Google Scholar 

  9. Dykes IM, Emanueli C. Transcriptional and post-transcriptional gene regulation by long non-coding RNA. Genom Proteom Bioinf. 2017;15(3):177–86.

    Article  Google Scholar 

  10. Li W, Chen Y, Nie X. Regulatory mechanisms of lncRNAs and their target gene signaling pathways in laryngeal squamous cell carcinoma. Front Pharmacol. 2020;11:1140.

    Article  CAS  Google Scholar 

  11. Cossu AM, Mosca L, Zappavigna S, Misso G, Bocchetti M, De Micco F, et al. Long non-coding RNAs as important biomarkers in laryngeal cancer and other head and neck tumours. Int J Mol Sci. 2019;20(14):3444.

    Article  CAS  Google Scholar 

  12. Wu Y, Zhang Y, Zheng X, Dai F, Lu Y, Dai L, et al. Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis. Mol Cancer. 2020;19(1):99.

    Article  CAS  Google Scholar 

  13. Wu Y, Zhang Y, Niu M, Shi Y, Liu H, Yang D, et al. Whole-transcriptome analysis of CD133+CD144+ cancer stem cells derived from human laryngeal squamous cell carcinoma cells. Cell Physiol Biochem. 2018;47(4):1696–710.

    Article  CAS  Google Scholar 

  14. Fabre AL, Colotte M, Luis A, Tuffet S, Bonnet J. An efficient method for long-term room temperature storage of RNA. Eur J Hum Genet. 2014;22(3):379–85.

    Article  CAS  Google Scholar 

  15. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-∆∆C(T)) method. Methods. 2001;25(4):402–8.

    Article  CAS  Google Scholar 

  16. Zhang XC, Liang ZY, Wang SY, Lu S, Song Y, Cheng Y, et al. Application of next-generation sequencing technology to precision medicine in cancer: joint consensus of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology. Cancer Biol Med. 2019;2:189–204.

    Google Scholar 

  17. Pallasch FB, Schumacher U. Angiotensin Inhibition, TGF-β and EMT in Cancer. Cancers. 2020;12(10):E2785.

    Article  Google Scholar 

  18. Zhao X, Yu D, Yang J, Xue K, Liu Y, Jin C. Knockdown of Snail inhibits epithelial-mesenchymal transition of human laryngeal squamous cell carcinoma Hep-2 cells through the vitamin D receptor signaling pathway. Biochem Cell Biol. 2017;95(6):672–8.

    Article  CAS  Google Scholar 

  19. Mosca L, Minopoli M, Pagano M, Vitiello F, Vincenza M, Carriero MV, et al. Effects of S-adenosyl-l-methionine on the invasion and migration of head and neck squamous cancer cells and analysis of the underlying mechanisms. Int J Onco. 2020;56(5):1212–24.

    CAS  Google Scholar 

  20. Zhu GJ, Song PP, Zhou H, Shen XH, Wang JG, Ma XF, et al. Role of epithelial-mesenchymal transition markers E-cadherin, N-cadherin, β-catenin and ZEB2 in laryngeal squamous cell carcinoma. Oncol Lett. 2018;15(3):3472–81.

    PubMed  PubMed Central  Google Scholar 

  21. Gao W, Zhang C, Li W, Li H, Sang J, Zhao Q, et al. Promoter methylation-regulated miR-145-5p inhibits laryngeal squamous cell carcinoma progression by targeting FSCN1. Mol Ther. 2019;27(2):365–79.

    Article  CAS  Google Scholar 

  22. Li J, Meng H, Bai Y, Wang K. Regulation of lncRNA and its role in cancer metastasis. Oncol Res. 2016;23(5):205–17.

    Article  Google Scholar 

  23. Cantile M, Di Bonito M, Cerrone M, Collina F, De Laurentiis M, Botti G. Long non-coding RNA HOTAIR in breast cancer therapy. Cancers (Basel). 2020;12(5):1197.

    Article  CAS  Google Scholar 

  24. Ghafouri-Fard S, Esmaeili M, Taheri M. H19 lncRNA: roles in tumorigenesis. Biomed Pharmacother. 2020;123:109774.

    Article  CAS  Google Scholar 

  25. Zhang C, Shao S, Zhang Y, Wang L, Liu J, Fang F, et al. LncRNA PCAT1 promotes metastasis of endometrial carcinoma through epigenetical downregulation of E-cadherin associated with methyltransferase EZH2. Life Sci. 2020;243:117295.

    Article  CAS  Google Scholar 

  26. Li CH, Chen YC. Targeting long non-coding RNAs in cancers: progress and prospects. Int J Biochem Cell Biol. 2013;45(8):1895–910.

    Article  CAS  Google Scholar 

  27. Qu LM, Jin M, Yang LK, Sun CH, Wang P, Li YS, et al. Expression of long non-coding RNA HOXA11-AS is correlated with progression of laryngeal squamous cell carcinoma. Am J Transl Res. 2018;10(2):573–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Chen L, Xu Z, Zhao J, Zhai X, Li J, Zhang Y, et al. H19/miR-107/HMGB1 axis sensitizes laryngeal squamous cell carcinoma to cisplatin by suppressing autophagy in vitro and in vivo. Cell Biol Int. 2021;45(3):674–85.

    Article  CAS  Google Scholar 

  29. Li R, Chen S, Zhan J, Li X, Liu W, Sheng X, et al. Long noncoding RNA FOXD2-AS1 enhances chemotherapeutic resistance of laryngeal squamous cell carcinoma via STAT3 activation. Cell Death Dis. 2020;11(1):41.

    Article  Google Scholar 

  30. Cao J, Yang Z, An R, Zhang J, Zhao R, Li W, et al. lncRNA IGKJ2-MALLP2 suppresses LSCC proliferation, migration, invasion, and angiogenesis by sponging miR-1911-3p/p21. Cancer Sci. 2020;111(9):3245–57.

    Article  CAS  Google Scholar 

  31. Wang R, Ma Z, Feng L, Yang Y, Tan C, Shi Q, et al. LncRNA MIR31HG targets HIF1A and P21 to facilitate head and neck cancer cell proliferation and tumorigenesis by promoting cell-cycle progression. Mol Cancer. 2018;17(1):162.

    Article  CAS  Google Scholar 

  32. Gugnoni M, Ciarrocchi A. Long noncoding RNA and epithelial mesenchymal transition in cancer. Int J Mol Sci. 2019;20(8):1924.

    Article  CAS  Google Scholar 

  33. Atefeh T, Mohsen M, Alireza M, Hassan MM, Mazaher A, Abolfazl A. Biological and clinical relevance of metastasis-associated long noncoding RNAs in esophageal squamous cell carcinoma: a systematic review. J Cell Physiol. 2020;2:848–68.

    Google Scholar 

  34. Monteiro-Reis S, Lobo J, Henrique R, Jerónimo C. Epigenetic mechanisms influencing epithelial to mesenchymal transition in bladder cancer. Int J Mol Sci. 2019;20(2):297.

    Article  Google Scholar 

  35. Wang H, Qian J, Xia X, Ye B. Long non-coding RNA OIP5-AS1 serves as an oncogene in laryngeal squamous cell carcinoma by regulating miR-204-5p/ZEB1 axis. N-S Arch Pharmacol. 2020. https://doi.org/10.1007/s00210-020-01811-7.

    Article  Google Scholar 

  36. Cui W, Meng W, Zhao L, Cao H, Chi W, Wang B. TGF-β-induced long non-coding RNA MIR155HG promotes the progression and EMT of laryngeal squamous cell carcinoma by regulating the miR-155-5p/SOX10 axis. Int J Oncol. 2019;54(6):2005–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Tong YX, Wang MH, Dai YN, Bao DJ, Zhang JJ, Pan HY. LncRNA HOXA-AS3 sponges miR-29c to facilitate cell proliferation, metastasis, and EMT process and activate the MEK/ERK signaling pathway in hepatocellular carcinoma. Hum Gene Ther Clin Dev. 2019;30(3):129–41.

    Article  CAS  Google Scholar 

  38. Zheng TL, Zhang X, Wang DW, Xu J, Kou KJ, Wang ZW, et al. Overexpressed lncRNA GATA6-AS1 inhibits LNM and EMT via FZD4 through the Wnt/β-catenin signaling pathway in GC. Mol Ther-Nucl Acids. 2020;19(3):827–40.

    Google Scholar 

  39. Lan L, Cao H, Chi W, Meng WX, Zhao L, Cui W, et al. Aberrant DNA hypermethylation-silenced LINC00886 gene accelerates malignant progression of laryngeal carcinoma. Pathol Res Pract. 2020;13:152877.

    Article  Google Scholar 

  40. Dhamija S, Diederichs S. From junk to master regulators of invasion: lncRNA functions in migration. EMT and metastasis Int J Cancer. 2016;139(2):269–80.

    Article  CAS  Google Scholar 

Download references

Funding

The study was funded by The Science and Technology Innovation Program for Colleges and Universities of Shanxi Education Department (Grant No. 2019L0411) and The National Natural Science Foundation of China (Gsrant No. 81902513).

Author information

Author notes

  1. H. Wu and W. Wang authors contributed equally to this work.

Authors and Affiliations

  1. School of Basic Medical Science, Shanxi Medical University, Jinzhong, Shanxi, 030600, P.R. China

    H. Wu, W. Wang & J. Zhu

Authors
  1. H. Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HW designed the study and wrote the manuscript. WW and JZ performed the experiments and statistical analyses. All authors read and approved the final manuscript.

Corresponding author

Correspondence to J. Zhu.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

Not applicable.

Informed consent

For this type of study, formal consent is not required.

Patient consent for publication

Not applicable.

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

Wu, H., Wang, W. & Zhu, J. Knockdown of long non-coding RNA RP11-297P16.3 inhibits the migration and invasion of laryngeal squamous carcinoma cells. Clin Transl Oncol 23, 2057–2065 (2021). https://doi.org/10.1007/s12094-021-02609-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-021-02609-6

Keywords

Search

Navigation