Skip to main content

Advertisement

Log in

Long noncoding RNA MGC27382 inhibits proliferation and metastasis of non-small cell lung cancer cells via down-regulating AKT/GSK3β pathway

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

Abstract

Purpose

Persistent abnormal proliferation and long distant metastasis of tumors contribute to high mortality rate in non-small cell lung cancer (NSCLC) patients. Strategies that prevent NSCLC proliferation and/or metastasis have been studied but still need to be further explored. Numerous studies have proved the diversity functions of long noncoding RNAs (lncRNAs) exerted in cancer, including NSCLC. In this study, we aim to identify and investigate the role of novel lncRNAs in NSCLC progression.

Methods

RNA sequence data were retrieved from the Cancer Genome Atlas (TCGA), differentially expressed lncRNAs (DElncRNAs) were screened out based on the R language, then real-time PCR experiment was introduced to detect the DElncRNA expression levels. A series of experiments including MTT, cell cycle, transwell, and wound healing assays were employed to explore the effect of DElncRNA MGC27382 on cell proliferation and invasion ability.

Results

We detected that DElncRNA MGC27382 is down-regulated in NSCLC tissues and cells. Overexpression of MGC27382 prevented NSCLC cell proliferation via down-regulating cyclin D1 and cyclin E. Moreover, wound healing and transwell assays indicated that the ability of cell invasion and migration could be impaired when cells were treated with MGC27382 overexpression. Further studies demonstrated that MGC27382-mediated inhibition on NSCLC progression can be impaired by LY294002, which is a frequently used inhibitor of AKT/GSK3β pathway.

Conclusion

MGC27382 is down-regulated in NSCLC. It exerts an inhibitory role in NSCLC development through suppressing the AKT/GSK3β pathway. Our results indicate that the lncRNA MGC27382 might be a tumor-suppressor gene in NSCLC. Overexpression of MGC27382 is thought to be a potential strategy for overcoming NSCLC progression.

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
Fig. 5

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this published article.

References

  1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.

    Article  Google Scholar 

  2. Lemjabbar-Alaoui H, Hassan OU, Yang YW, et al. Lung cancer: biology and treatment options. Biochim Biophys Acta. 2015;1856:189–210.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Youlden DR, Cramb SM, Baade PD. The international epidemiology of lung cancer: geographical distribution and secular trends. J Thorac Oncol. 2008;3:819–31.

    Article  Google Scholar 

  4. Mattick JS. The genetic signatures of noncoding RNAs. PLoS Genet. 2009;5: e1000459.

    Article  Google Scholar 

  5. Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;43:904–14.

    Article  CAS  Google Scholar 

  6. Tsai MC, Manor O, Wan Y, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010;329:689–93.

    Article  CAS  Google Scholar 

  7. Schmitt AM, Chang HY. Long noncoding RNAs in cancer pathways. Cancer Cell. 2016;29:452–63.

    Article  CAS  Google Scholar 

  8. Chen J, Wang R, Zhang K, et al. Long non-coding RNAs in non-small cell lung cancer as biomarkers and therapeutic targets. J Cell Mol Med. 2014;18:2425–36.

    Article  CAS  Google Scholar 

  9. Nie W, Ge HJ, Yang XQ, et al. LncRNA-UCA1 exerts oncogenic functions in non-small cell lung cancer by targeting miR-193a-3p. Cancer Lett. 2016;371:99–106.

    Article  CAS  Google Scholar 

  10. Wan L, Sun M, Liu GJ, et al. Long noncoding RNA PVT1 promotes non-small cell lung cancer cell proliferation through epigenetically regulating LATS2 expression. Mol Cancer Ther. 2016;15:1082–94.

    Article  CAS  Google Scholar 

  11. Lu W, Zhang H, Niu Y, et al. Long non-coding RNA linc00673 regulated non-small cell lung cancer proliferation, migration, invasion and epithelial mesenchymal transition by sponging miR-150-5p. Mol Cancer. 2017;16:118.

    Article  Google Scholar 

  12. Wang H, Niu L, Jiang S, et al. Comprehensive analysis of aberrantly expressed profiles of lncRNAs and miRNAs with associated ceRNA network in muscle-invasive bladder cancer. Oncotarget. 2016;7:86174–85.

    Article  Google Scholar 

  13. Niu L, Deng J, Zhu F, et al. Anti-inflammatory effect of Marchantin M contributes to sensitization of prostate cancer cells to docetaxel. Cancer Lett. 2014;348:126–34.

    Article  CAS  Google Scholar 

  14. Wang W, He X, Zheng Z, et al. Serum HOTAIR as a novel diagnostic biomarker for esophageal squamous cell carcinoma. Mol Cancer. 2017;16:75.

    Article  CAS  Google Scholar 

  15. Wu D, Li Y, Zhang H, et al. Knockdown of Lncrna PVT1 enhances radiosensitivity in non-small cell lung cancer by sponging Mir-195. Cell Physiol Biochem. 2017;42:2453–66.

    Article  CAS  Google Scholar 

  16. Chen W, Zhu H, Yin L, et al. lncRNA-PVT1 facilitates invasion through upregulation of MMP9 in nonsmall cell lung cancer cell. DNA Cell Biol. 2017;36:787–93.

    Article  CAS  Google Scholar 

  17. Merchant N, Nagaraju GP, Rajitha B, et al. Matrix metalloproteinases: their functional role in lung cancer. Carcinogenesis. 2017;38:766–80.

    Article  CAS  Google Scholar 

  18. Chen WF, Gao WD, Li QL, et al. SLIT2 inhibits cell migration in colorectal cancer through the AKT-GSK3beta signaling pathway. Int J Colorectal Dis. 2013;28:933–40.

    Article  Google Scholar 

  19. Gao F, Huang W, Zhang Y, et al. Hes1 promotes cell proliferation and migration by activating Bmi-1 and PTEN/Akt/GSK3beta pathway in human colon cancer. Oncotarget. 2015;6:38667–80.

    Article  Google Scholar 

  20. Lu KH, Li W, Liu XH, et al. Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer. 2013;13:461.

    Article  Google Scholar 

  21. Sun M, Liu XH, Wang KM, et al. Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial-mesenchymal transition. Mol Cancer. 2014;13:68.

    Article  Google Scholar 

  22. Liu Z, Sun M, Lu K, et al. The long noncoding RNA HOTAIR contributes to cisplatin resistance of human lung adenocarcinoma cells via downregualtion of p21(WAF1/CIP1) expression. PLoS ONE. 2013;8: e77293.

    Article  CAS  Google Scholar 

  23. Weber DG, Johnen G, Casjens S, et al. Evaluation of long noncoding RNA MALAT1 as a candidate blood-based biomarker for the diagnosis of non-small cell lung cancer. BMC Res Notes. 2013;6:518.

    Article  Google Scholar 

  24. Han L, Kong R, Yin DD, et al. Low expression of long noncoding RNA GAS6-AS1 predicts a poor prognosis in patients with NSCLC. Med Oncol. 2013;30:694.

    Article  Google Scholar 

  25. Tseng RC, Lee SH, Hsu HS, et al. SLIT2 attenuation during lung cancer progression deregulates beta-catenin and E-cadherin and associates with poor prognosis. Cancer Res. 2010;70:543–51.

    Article  CAS  Google Scholar 

  26. Liao K, Li J, Wang Z. Dihydroartemisinin inhibits cell proliferation via AKT/GSK3beta/cyclinD1 pathway and induces apoptosis in A549 lung cancer cells. Int J Clin Exp Pathol. 2014;7:8684–91.

    PubMed  PubMed Central  Google Scholar 

  27. Liu XH, Liu ZL, Sun M, et al. The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer. BMC Cancer. 2013;13:464.

    Article  Google Scholar 

  28. Yang YR, Zang SZ, Zhong CL, et al. Increased expression of the lncRNA PVT1 promotes tumorigenesis in non-small cell lung cancer. Int J Clin Exp Pathol. 2014;7:6929–35.

    PubMed  PubMed Central  Google Scholar 

  29. Cui D, Yu CH, Liu M, et al. Long non-coding RNA PVT1 as a novel biomarker for diagnosis and prognosis of non-small cell lung cancer. Tumour Biol. 2016;37:4127–34.

    Article  CAS  Google Scholar 

  30. Loewen G, Jayawickramarajah J, Zhuo Y, et al. Functions of lncRNA HOTAIR in lung cancer. J Hematol Oncol. 2014;7:90.

    Article  Google Scholar 

  31. Liao M, Li B, Zhang S, et al. Relationship between LINC00341 expression and cancer prognosis. Oncotarget. 2017;8:15283–93.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the China Postdoctoral Science Foundation (No. 2018M630786) and the National Natural Science Foundation of China (No. 82002540).

Author information

Authors and Affiliations

Authors

Contributions

QL designed the study and drafted the manuscript. LLN, SLY, HMN, and SL were responsible for the collection and analysis of the experimental data. CCL revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to C. Cheng.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethical Committee of Qilu Hospital of Shandong University and conducted in accordance with the ethical standards.

Informed consent

Yes.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 62 KB)

Supplementary file2 (XLSX 45 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Q., Li, S., Niu, L. et al. Long noncoding RNA MGC27382 inhibits proliferation and metastasis of non-small cell lung cancer cells via down-regulating AKT/GSK3β pathway. Clin Transl Oncol 23, 2548–2559 (2021). https://doi.org/10.1007/s12094-021-02658-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-021-02658-x

Keywords

Navigation