Skip to main content

Advertisement

SpringerLink
Log in

LINC02381-ceRNA exerts its oncogenic effect through regulation of IGF1R signaling pathway in glioma

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Purpose

LncRNAs play essential roles in the cellular and molecular biology of glioma. Some LncRNAs exert their role through sponging miRNAs and regulating multiple signaling pathways. LINC02381 is involved in several cancer types as either oncogene or tumor suppressor. Here, we intended to find the molecular mechanisms of the LINC02381 effect during the glioma progression in related cell lines.

Methods and results

RNA-seq data analysis indicated the oncogenic characteristics of LINC02381, and RT-qPCR results confirmed its upregulation compared to normal tissues. Besides its expression was relatively stronger in invasive glioma cell lines. Furthermore, in silico analysis revealed LINC02381 is concentrated in the cytoplasm and predicted its sponging effect against miR-128 and miR-150, which was verified through dual luciferase assay. When LINC02381 was overexpressed in 1321N1, U87, and A172 cell lines, IGF1R and TrkC receptors as well as their downstream pathways (PI3K and RAS/MAPK), were upregulated, detected by RT-qPCR, and verified by western analysis. Consistently, LINC02381 overexpression was followed by an increased proliferation rate of transfected glioma cell lines, detected by flow cytometry and MTT assay, and RT-qPCR. It also resulted in elevated EMT and stemness markers expression level, increased migration rate, and reduced apoptosis rate, detected by RT-qPCR, western analysis, scratch test, and Annexin/PI flow cytometry analysis, respectively.

Conclusion

The overall results indicated that LINC02381 exerts its oncogenic effect in glioma cells through sponging miR-128 and miR-150 to upregulate the IGF1R signaling pathway. Our results introduce LINC02381 and miR-128, and miR-150 as potential prognosis and therapy targets for the treatment of glioma.

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
Fig. 7

Similar content being viewed by others

Data availability

“The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Louis DN et al (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131(6):803–820

    Article  PubMed  Google Scholar 

  2. Ma Q et al (2018) Cancer stem cells and immunosuppressive microenvironment in glioma. Front Immunol 9:2924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359(5):492–507

    Article  CAS  PubMed  Google Scholar 

  4. DeSouza PA et al (2021) Long, noncoding RNA dysregulation in glioblastoma. Cancers 13(7):1604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gao Y-F et al (2016) A critical overview of long non-coding RNA in glioma etiology 2016: an update. Tumor Biology 37(11):14403–14413

    Article  CAS  PubMed  Google Scholar 

  6. Jiang M-C et al (2019) Emerging roles of lncRNA in cancer and therapeutic opportunities. Am J Cancer Res 9(7):1354

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Yeh M et al (2021) MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44. Sci Rep 11(1):1–11

    Article  CAS  Google Scholar 

  8. Shan Z-N et al (2016) miR128-1 inhibits the growth of glioblastoma multiforme and glioma stem-like cells via targeting BMI1 and E2F3. Oncotarget 7(48):78813

    Article  PubMed  PubMed Central  Google Scholar 

  9. Peng Y, Croce CM (2016) The role of MicroRNAs in human cancer. Signal Transduct Target Ther 1(1):1–9

    Article  Google Scholar 

  10. Li Q et al (2016) LncRNA and mRNA expression profiles of glioblastoma multiforme (GBM) reveal the potential roles of lncRNAs in GBM pathogenesis. Tumor Biol 37(11):14537–14552

    Article  CAS  Google Scholar 

  11. Kazimierczyk M et al (2020) Human long noncoding RNA interactome: detection, characterization and function. Int J Mol Sci 21(3):1027

    Article  CAS  PubMed Central  Google Scholar 

  12. Mu M et al (2020) LncRNA BCYRN1 inhibits glioma tumorigenesis by competitively binding with miR-619-5p to regulate CUEDC2 expression and the PTEN/AKT/p21 pathway. Oncogene 39(45):6879–6892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Li Z et al (2017) Long non-coding RNA MALAT1 promotes proliferation and suppresses apoptosis of glioma cells through derepressing Rap1B by sponging miR-101. J Neurooncol 134(1):19–28

    Article  CAS  PubMed  Google Scholar 

  14. Wang P et al (2015) Long non-coding RNA CASC2 suppresses malignancy in human gliomas by miR-21. Cell Signal 27(2):275–282

    Article  CAS  PubMed  Google Scholar 

  15. Kim S-H et al (2021) Long non-coding RNAs in brain tumors: roles and potential as therapeutic targets. J Hematol Oncol 14(1):1–17

    Article  CAS  Google Scholar 

  16. Shi T et al (2020) HOTAIRM1, an enhancer lncRNA, promotes glioma proliferation by regulating long-range chromatin interactions within HOXA cluster genes. Mol Biol Rep 47(4):2723–2733

    Article  CAS  PubMed  Google Scholar 

  17. Feng W et al (2017) Up-regulation of the long non-coding RNA RMRP contributes to glioma progression and promotes glioma cell proliferation and invasion. Arch Med Sci 13(6):1315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cai H et al (2020) LncRNA LINC00998 inhibits the malignant glioma phenotype via the CBX3-mediated c-Met/Akt/mTOR axis. Cell Death Dis 11(12):1–17

    Article  CAS  Google Scholar 

  19. Ke J et al (2015) Knockdown of long non-coding RNA HOTAIR inhibits malignant biological behaviors of human glioma cells via modulation of miR-326. Oncotarget 6(26):21934

    Article  PubMed  PubMed Central  Google Scholar 

  20. Li Y et al (2021) LncRNA NEAT1 promotes glioma cancer progression via regulation of miR-98-5p/BZW1. Biosci Rep

  21. Liu Z et al (2020) LncRNA H19 promotes glioma angiogenesis through miR-138/HIF-1α/VEGF axis. Neoplasma 67(1):111–118

    Article  CAS  PubMed  Google Scholar 

  22. Jia P et al (2016) Long non-coding RNA H19 regulates glioma angiogenesis and the biological behavior of glioma-associated endothelial cells by inhibiting microRNA-29a. Cancer Lett 381(2):359–369

    Article  CAS  PubMed  Google Scholar 

  23. Jafarzadeh M et al (2020) Epigenetically silenced LINC02381 functions as a tumor suppressor by regulating PI3K-Akt signaling pathway. Biochimie 171:63–71

    Article  PubMed  CAS  Google Scholar 

  24. Jafarzadeh M, Soltani BM (2020) Long noncoding RNA LOC400043 (LINC02381) inhibits gastric cancer progression through regulating Wnt signaling pathway. Front Oncol 10:2189

    Article  Google Scholar 

  25. Bian X et al (2021) ELK1-induced upregulation lncRNA LINC02381 accelerates the osteosarcoma tumorigenesis through targeting CDCA4 via sponging miR-503–5p. Biochem Biophys Res Commun 548:112–119

    Article  CAS  PubMed  Google Scholar 

  26. Chen X et al (2020) LINC02381 promoted Cell viability and migration via targeting miR-133b in cervical cancer cells. Cancer Manag Res 12:3971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sun Y, Wang X, Bu X (2021) LINC02381 contributes to cell proliferation and hinders cell apoptosis in glioma by transcriptionally enhancing CBX5. Brain Res Bull 176:121–129

    Article  CAS  PubMed  Google Scholar 

  28. Shan Y et al (2018) LncRNA SNHG7 sponges miR-216b to promote proliferation and liver metastasis of colorectal cancer through upregulating GALNT1. Cell Death Dis 9(7):1–13

    Article  CAS  Google Scholar 

  29. Xu M et al (2019) lncRNA SNHG6 regulates EZH2 expression by sponging miR-26a/b and miR-214 in colorectal cancer. J Hematol Oncol 12(1):1–17

    Article  Google Scholar 

  30. Salmena L et al (2011) A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146(3):353–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Du Z, Lovly CM (2018) Mechanisms of receptor tyrosine kinase activation in cancer. Mol Cancer 17(1):1–13

    Article  CAS  Google Scholar 

  32. Zhang Q et al (2021) FoxP3-miR-150-5p/3p suppresses ovarian tumorigenesis via an IGF1R/IRS1 pathway feedback loop. Cell Death Dis 12(3):1–16

    Article  PubMed  PubMed Central  Google Scholar 

  33. Chen P-H et al (2016) The inhibition of microRNA-128 on IGF-1-activating mTOR signaling involves in temozolomide-induced glioma cell apoptotic death. PLoS ONE 11(11):e0167096

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Peruzzi F et al (1999) Multiple signaling pathways of the insulin-like growth factor 1 receptor in protection from apoptosis. Mol Cell Biol 19(10):7203–7215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Guidi M et al (2010) Overexpression of miR-128 specifically inhibits the truncated isoform of NTRK3 and upregulates BCL2 in SH-SY5Y neuroblastoma cells. BMC Mol Biol 11(1):1–17

    Article  CAS  Google Scholar 

  36. Pollak MN, Schernhammer ES, Hankinson SE (2004) Insulin-like growth factors and neoplasia. Nat Rev Cancer 4(7):505–518

    Article  CAS  PubMed  Google Scholar 

  37. Huo L et al (2019) miR-128-3p inhibits glioma cell proliferation and differentiation by targeting NPTX1 through IRS-1/PI3K/AKT signaling pathway. Exp Ther Med 17(4):2921–2930

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Huang C-Y et al (2015) miR-128-3p suppresses hepatocellular carcinoma proliferation by regulating PIK3R1 and is correlated with the prognosis of HCC patients. Oncol Rep 33(6):2889–2898

    Article  CAS  PubMed  Google Scholar 

  39. Zhuang M et al (2021) LncRNA Bmp1 promotes the healing of intestinal mucosal lesions via the miR-128-3p/PHF6/PI3K/AKT pathway. Cell Death Dis 12(6):1–16

    Article  CAS  Google Scholar 

  40. Liu X et al (2020) Nanocomplexes loaded with miR-128-3p for enhancing chemotherapy effect of colorectal cancer through dual-targeting silence the activity of PI3K/AKT and MEK/ERK pathway. Drug Deliv 27(1):323–333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wu SJ et al (2018) MicroRNA-150 enhances radiosensitivity by inhibiting the AKT pathway in NK/T cell lymphoma. J Exp Clin Cancer Res 37(1):1–10

    Article  CAS  Google Scholar 

  42. Zhao J, Li D, Fang L (2019) MiR-128-3p suppresses breast cancer cellular progression via targeting LIMK1. Biomed Pharmacother 115:108947

    Article  CAS  PubMed  Google Scholar 

  43. Cao X-Z, Bin H, Zang Z-N (2019) MiR-128 suppresses the growth of thyroid carcinoma by negatively regulating SPHK1. Biomed Pharmacother 109:1960–1966

    Article  CAS  PubMed  Google Scholar 

  44. Shi Z-M et al (2012) MiR-128 inhibits tumor growth and angiogenesis by targeting p70S6K1. PLoS ONE 7(3):e32709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Tan Z, Jia J, Jiang Y (2018) MiR-150-3p targets SP1 and suppresses the growth of glioma cells. Biosci Rep 38(3)

  46. Lian B et al (2018) miR-128 targets the SIRT1/ROS/DR5 pathway to sensitize colorectal cancer to TRAIL-induced apoptosis. Cell Physiol Biochem 49(6):2151–2162

    Article  CAS  PubMed  Google Scholar 

  47. Han H et al (2018) miR-128 induces pancreas cancer cell apoptosis by targeting MDM4. Exp Ther Med 15(6):5017–5022

    PubMed  PubMed Central  Google Scholar 

  48. Ye Y et al (2018) MiR-128 promotes the apoptosis of glioma cells via binding to NEK2. Eur Rev Med Pharmacol Sci 22(24):8781–8788

    CAS  PubMed  Google Scholar 

  49. Shang C et al (2016) miR-128 regulates the apoptosis and proliferation of glioma cells by targeting RhoE. Oncol Lett 11(1):904–908

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  Google Scholar 

  51. Liu X et al (2016) MicroRNA-128 inhibits EMT of human osteosarcoma cells by directly targeting integrin α2. Tumor Biol 37(6):7951–7957

    Article  CAS  Google Scholar 

  52. Zhao C et al (2020) MicroRNA-128-3p enhances the chemosensitivity of temozolomide in glioblastoma by targeting c-Met and EMT. Sci Rep 10(1):1–12

    CAS  Google Scholar 

  53. Cao D et al (2020) MiR-128 suppresses metastatic capacity by targeting metadherin in breast cancer cells. Biol Res 53(1):1–13

    Article  CAS  Google Scholar 

  54. Hong X, Yu J-J (2019) MicroRNA-150 suppresses epithelial-mesenchymal transition, invasion, and metastasis in prostate cancer through the TRPM4-mediated β-catenin signaling pathway. Am J Physiol Cell Physiol 316(4):C463–C480

    Article  CAS  PubMed  Google Scholar 

  55. Dai F-Q et al (2019) miR-150-5p inhibits non-small-cell lung cancer metastasis and recurrence by targeting HMGA2 and β-catenin signaling. Mol Ther-Nucleic Acids 16:675–685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhang PF et al (2019) LncRNA SNHG3 induces EMT and sorafenib resistance by modulating the miR-128/CD151 pathway in hepatocellular carcinoma. J Cell Physiol 234(3):2788–2794

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are thankful for the help and advice of the 4402-laboratory members at the Department of Genetics, TMU. Tehran-Iran.

Funding

This study was supported by Tarbiat Modares University and NIGEB.

Author information

Authors and Affiliations

  1. Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Hossein Nemati, Amir-Reza Javanmard, Seyed Javad Mowla & Bahram M. Soltani

  2. National Institute of Genetics Engineering and Biotechnology (NIGEB), Tehran, Iran

    Hossein Nemati & Masoumeh Fakhre-Taha

  3. Stem Cell and Regenerative Medicine Research Centre, Iran University of Medical Sciences (IUMS), Tehran, Iran

    Amin Jahanbakhshi

  4. School of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Bahram M. Soltani

Authors
  1. Hossein Nemati
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masoumeh Fakhre-Taha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amir-Reza Javanmard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amin Jahanbakhshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seyed Javad Mowla
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bahram M. Soltani
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HN performed the experiments. HN and BMS designed the experiments. BMS and MFT supervised the study. ARJ has helped with lab work. AJ provided the tissues and pathology information. SJM advised the research.

Corresponding author

Correspondence to Bahram M. Soltani.

Ethics declarations

Competing interest

The authors declare that they have no competing interests.

Ethics approval

This study was approved by the Ethical/Scientific Committee of Tarbiat Modares University under; IR.MODARES.REC.1400.129.

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 (RAR 49893 kb)

Supplementary file2 (DOC 35 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nemati, H., Fakhre-Taha, M., Javanmard, AR. et al. LINC02381-ceRNA exerts its oncogenic effect through regulation of IGF1R signaling pathway in glioma. J Neurooncol 158, 1–13 (2022). https://doi.org/10.1007/s11060-022-03992-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-022-03992-y

Keywords

Search

Navigation