Investigating the Role of T-cell-associated Lncrnas in Glioblastoma Recurrence Using Single-cell RNA Sequencing Analysis

Document Type : Original Article (s)

Authors

1 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

2 Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

3 Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran

10.48305/jims.v43.i836.1373

Abstract

Background: Glioblastoma (GBM) is one of the primary malignant tumors of the central nervous system. Surgical limitations and resistance to therapy are important challenges in its treatment. This cancer has a high recurrence rate due to genetic heterogeneity, the presence of cancer stem cells (CSCs), and a unique tumor microenvironment (TME). The aim of this study is to identify lncRNAs associated with cells involved in recurrence and to investigate their role in regulating the immune response and related mechanisms using bioinformatic analysis of single-cell RNA data.
Methods: In this study, the differences in lncRNA expression among various cell types in primary and recurrent GBM were investigated using single-cell RNA sequencing (scRNA-seq) analysis. Data analysis was performed using the SingleR package. Cells were classified into four distinct types based on gene expression patterns. Among these, T cells were selected for further study due to their key role in the tumor microenvironment and immune response.
Findings: The different cells were categorized into 4 distinct types based on their gene expression profiles. Among these types, T cells were selected due to their pivotal role in the tumor microenvironment and immunity. The results revealed that 11 lncRNAs, including LINC01088, PVT1, and KCNQ1OT1, exhibited different expression levels in T cells between primary and recurrent GBM.
Conclusion: This study provides new insights into the differences in gene expression between primary and recurrent GBM and highlights the potential of lncRNAs as therapeutic targets. It is likely that these lncRNAs play a role in glioblastoma formation and recurrence by regulating cancer-related gene expression and pathways. Definitive and final conclusions require further complementary studies.

Highlights

Morteza Hadizadeh: PubMed

Sorayya Ghasemi:  PubMed ,Google Scholar

Keywords

Main Subjects

References

  1. Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA 2013; 310(17): 1842-50.
  2. Khasraw M, Fujita Y, Lee-Chang C, Balyasnikova IV, Najem H, Heimberger AB. New approaches to glioblastoma. Annu Rev Med 2022; 73(1): 279-92.
  3. Ostrom QT, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2013–2017. Neuro Oncol 2020; 22(Suppl 1): iv1-iv96.
  4. Birzu C, French P, Caccese M, Cerretti G, Idbaih A, Zagonel V, et al. Recurrent glioblastoma: from molecular landscape to new treatment perspectives. Cancers (Basel)2020; 13(1): 47.
  5. Perdyan A, Lawrynowicz U, Horbacz M, Kaminska B, Mieczkowski J. Integration of single-cell RNA sequencing and spatial transcriptomics to reveal the glioblastoma heterogeneity. F1000Res 2023; 11: 1180.
  6. Johnson BE, Mazor T, Hong C, Barnes M, Aihara K, McLean CY, et al. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science 2014; 343(6167): 189-93.
  7. Trapnell C. Defining cell types and states with single-cell genomics. Genome Res 2015; 25(10): 1491-8.
  8. Magee JA, Piskounova E, Morrison SJ. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 2012; 21(3): 283-96.
  9. Arneth B. Tumor microenvironment. Medicina (Kaunas) 2019; 56(1): 15.
  10. Noor L, Upadhyay A, Joshi V. Role of T Lymphocytes in Glioma Immune Microenvironment: Two Sides of a Coin. Biology (Basel) 2024; 13(10): 846.
  11. Luecken MD, Theis FJ. Current best practices in single‐cell RNA‐seq analysis: a tutorial. Mol Syst Biol 2019; 15(6): e8746.
  12. Olsen TK, Baryawno N. Introduction to single‐cell RNA sequencing. Curr Protoc Mol Biol 2018; 122(1): e57.
  13. Stackhouse CT, Gillespie GY, Willey CD. Exploring the roles of lncRNAs in GBM pathophysiology and their therapeutic potential. Cells 2020; 9(11): 2369.
  14. Li Q, Jia H, Li H, Dong C, Wang Y, Zou Z. LncRNA and mRNA expression profiles of glioblastoma multiforme (GBM) reveal the potential roles of lncRNAs in GBM pathogenesis. Tumour Biol 2016; 37(11): 14537-52.
  15. Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck WM, et al. Comprehensive integration of single-cell data. Cell 2019; 177(7): 1888-902. e21.
  16. Aran D, Looney AP, Liu L, Wu E, Fong V, Hsu A, et al. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat Immunol 2019; 20(2): 163-72.
  17. Tian S, Liu J, Kong S, Peng L. LncRNA DLX6-AS1 as a potential molecular biomarker in the clinicopathology and prognosis of various cancers: a meta-analysis. Biosci Rep 2020; 40(8): BSR20193532.
  18. Lingadahalli S, Jadhao S, Sung YY, Chen M, Hu L, Chen X, et al. Novel lncRNA LINC00844 regulates prostate cancer cell migration and invasion through AR signaling. Mol Cancer Res 2018; 16(12): 1865-78.
  19. Guan Y, Bhandari A, Xia E, Yang F, Xiang J, Wang O. lncRNA FOXD3‐AS1 is associated with clinical progression and regulates cell migration and invasion in breast cancer. Cell Biochem Funct 2019; 37(4): 239-44.
  20. Kikuchi Y, Tokita S, Hirama T, Kochin V, Nakatsugawa M, Shinkawa T, et al. CD8+ T–cell immune surveillance against a tumor antigen encoded by the oncogenic long noncoding RNA PVT1. Cancer Immunol Res 2021; 9(11): 1342-53.
  21. Hu J, Qian Y, Peng L, Ma L, Qiu T, Liu Y, et al. Long noncoding RNA EGFR-AS1 promotes cell proliferation by increasing EGFR mRNA stability in gastric cancer. Cell Physiol Biochem 2018; 49(1): 322-34.
  22. Zhu D, Ouyang X, Zhang Y, Yu X, Su K, Li L. A promising new cancer marker: Long noncoding RNA EGFR-AS1. Front Oncol 2023; 13: 1130472.
  23. Zhu B, Liu W, Liu H, Xu Q, Xu W. LINC01094 down-regulates miR-330-3p and enhances the expression of MSI1 to promote the progression of glioma. Cancer Manag Res 2020: 6511-21.
  24. Xie Y, He L, Lugano R, Zhang Y, Cao H, He Q, et al. Key molecular alterations in endothelial cells in human glioblastoma uncovered through single-cell RNA sequencing. JCI insight 2021; 6(15): e150861.
  25. Yeo AT, Rawal S, Delcuze B, Christofides A, Atayde A, Strauss L, et al. Single-cell RNA sequencing reveals evolution of immune landscape during glioblastoma progression. Nat Immunol 2022; 23(6): 971-84.
  26. Jindal V. Role of chimeric antigen receptor T cell therapy in glioblastoma multiforme. Mol Neurobiol 2018; 55(11): 8236-42.
  27. Yu W, Ma Y, Hou W, Wang F, Cheng W, Qiu F, et al. Identification of immune-related lncRNA prognostic signature and molecular subtypes for glioblastoma. Front Immunol 2021; 12: 706936.
  28. Wang X, Gao M, Ye J, Jiang Q, Yang Q, Zhang C, et al. An immune gene-related five-lncRNA signature for to predict glioma prognosis. Front Genet 2020; 11: 612037.
  29. Sheykhhasan M, Ahmadyousefi Y, Seyedebrahimi R, Tanzadehpanah H, Manoochehri H, Dama P, et al. DLX6-AS1: a putative lncRNA candidate in multiple human cancers. Expert Rev Mol Med 2021; 23: e17.
  30. NcPath database. Available from: http://ncpath.pianlab.cn/.
  31. Zeng Z, Chen Y, Geng X, Zhang Y, Wen X, Yan Q, et al. NcRNAs: Multi‑angle participation in the regulation of glioma chemotherapy resistance. Int J Oncol 2022; 60(6): 76.
  32. Chae Y, Roh J, Kim W. The roles played by long non-coding RNAs in glioma resistance. Int J Mol Sci 2021; 22(13): 6834.
  33. Peng T, Chen D-L, Chen S-L. LINC01088 promotes the growth and invasion of glioma cells through regulating small nuclear ribonucleoprotein polypeptide A transcription. Bioengineered 2022; 13(4): 9172-83.
Journal of Isfahan Medical School
Volume 43, Issue 836
4th Week, December
November and December 2026
Pages 1373-1382

Files

History

  • Receive Date: 05 February 2025
  • Accept Date: 28 December 2025

Share

How to cite

Statistics