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Unveiling the Expression of UNC13C in Brain and Glioblastoma Cells

Year 2025, Volume: 15 Issue: 1, 198 - 202
https://doi.org/10.33808/clinexphealthsci.1573250

Abstract

Objective: Glioblastoma (GBM) is the most aggressive type of brain tumor, accounting approximately half of malignant central nervous system tumors. Median overall survival remains below 15 months post-diagnosis. Current treatments include surgical resection, radiotherapy, and chemotherapy, primarily with temozolomide, yet the median overall survival remains below 15 months post-diagnosis. Understanding the molecular mechanisms of GBM is essential for developing novel therapeutic approaches. Among the implicated genes, the UNC13 protein family, particularly UNC13C, is of interest. While UNC13A and UNC13B have been linked to various neurological disorders, UNC13C has been less studied despite its involvement in neurotransmitter release and potential tumor-suppressive effects in other cancers. Our previous work indicated low expression levels of UNC13C in glioblastoma cell lines compared to healthy brain tissue, suggesting a role in GBM pathogenesis. In this study, we aimed to comprehensively evaluate UNC13C expression using web based bioinformatics tools and experimental approaches.
Methods: We analyzed UNC13C expression across various tissues via Correlation Analyzer, confirming in glioblastoma tissues compared to healthy brain samples using the GEPIA and UALCAN databases. Additionally, we assessed UNC13C levels in glioblastoma cell lines (LN-18, A-172, U-87), human microglia (HMC3), and healthy astrocytes through quantitative real-time polymerase chain reaction (qRT-PCR).
Results: Our findings reveal that UNC13C expression is notably reduced in glioblastoma cells, with the highest expression observed in healthy astrocytes, albeit at low levels. These results underscore the importance of UNC13C in GBM and highlight the need for further investigation into its role in tumor development and progression.
Conclusion: This study provides the first report of UNC13C expression detailed in human cell lines both normal and glioblastoma, emphasizing its significance from a developmental perspective.

Ethical Statement

No requirements for ethical approval.

References

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  • Rajaratnam V, Islam MM, Yang M, Slaby R, Ramirez HM, Mirza SP. Glioblastoma: Pathogenesis and Current Status of Chemotherapy and Other Novel Treatments. Cancers (Basel). 2020 Apr 10;12(4):937. https://doi.org/10.3390/cancers12040937
  • Wesolowski JR, Rajdev P, Mukherji SK. Temozolomide (Temodar). AJNR Am J Neuroradiol. 2010 Sep;31(8):1383-4. https://doi.org/10.3174/ajnr.A2170
  • Ansari U, Chen V, Sedighi R, Syed B, Muttalib Z, Ansari K, Ansari F, Nadora D, Razick D, Lui F. Role of the UNC13 family in human diseases: A literature review. AIMS Neurosci. 2023 Dec 6;10(4):388-400. https://doi.org/10.3934/Neuroscience.2023029
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  • Aricò M, Boggio E, Cetica V, Melensi M, Orilieri E, Clemente N, Cappellano G, Buttini S, Soluri MF, Comi C, Dufour C, Pende D, Dianzani I, Ellis SR, Pagliano S, Marcenaro S, Ramenghi U, Chiocchetti A, Dianzani U. Variations of the UNC13D gene in patients with autoimmune lymphoproliferative syndrome. PLoS One. 2013 Jul 1;8(7):e68045. https://doi.org/10.1371/journal.pone.0068045
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  • Gulluoglu S, Tuysuz EC, Sahin M, Kuskucu A, Kaan Yaltirik C, Ture U, Kucukkaraduman B, Akbar MW, Gure AO, Bayrak OF, Dalan AB. Simultaneous miRNA and mRNA transcriptome profiling of glioblastoma samples reveals a novel set of OncomiR candidates and their target genes. Brain Res. 2018 Dec 1;1700:199-210. https://doi.org/10.1016/j.brainres.2018.08.035
  • Miller HE, Bishop AJR. Correlation AnalyzeR: functional predictions from gene co-expression correlations. BMC Bioinformatics. 2021 Apr 20;22(1):206. https://doi.org/10.1186/s12859-021-04130-7
  • Chandrashekar DS, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M, Netto GJ, Qin ZS, Kumar S, Manne U, Creighton CJ, Varambally S. UALCAN: An update to the integrated cancer data analysis platform. Neoplasia. 2022 Mar;25:18-27. https://doi.org/10.1016/j.neo.2022.01.001
  • Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017 Jul 3;45(W1):W98-W102. https://doi.org/10.1093/nar/gkx247
  • Augustin I, Korte S, Rickmann M, Kretzschmar HA, Südhof TC, Herms JW, Brose N. The cerebellum-specific Munc13 isoform Munc13-3 regulates cerebellar synaptic transmission and motor learning in mice. J Neurosci. 2001 Jan 1;21(1):10-7. https://doi.org/10.1523/JNEUROSCI.21-01-00010.2001
  • Meunier FA, Hu Z. Functional Roles of UNC-13/Munc13 and UNC-18/Munc18 in Neurotransmission. Adv Neurobiol. 2023;33:203-231. https://doi.org/10.1007/978-3-031-34229-5_8
  • Batiuk MY, Martirosyan A, Wahis J, de Vin F, Marneffe C, Kusserow C, Koeppen J, Viana JF, Oliveira JF, Voet T, Ponting CP, Belgard TG, Holt MG. Identification of region-specific astrocyte subtypes at single cell resolution. Nat Commun. 2020 Mar 5;11(1):1220. https://doi.org/10.1038/s41467-019-14198-8
  • Wang YY, Liu SC, Yang Z, Zhang T. Impaired hippocampal synaptic plasticity in C6 glioma-bearing rats. J Neurooncol. 2011 Jul;103(3):469-77. https://doi.org/10.1007/s11060-010-0447-7
  • Janabi N, Peudenier S, Héron B, Ng KH, Tardieu M. Establishment of human microglial cell lines after transfection of primary cultures of embryonic microglial cells with the SV40 large T antigen. Neurosci Lett. 1995 Aug 4;195(2):105-8. https://doi.org/10.1016/0304-3940(94)11792-h
Year 2025, Volume: 15 Issue: 1, 198 - 202
https://doi.org/10.33808/clinexphealthsci.1573250

Abstract

References

  • Batash R, Asna N, Schaffer P, Francis N, Schaffer M. Glioblastoma Multiforme, Diagnosis and Treatment; Recent Literature Review. Curr Med Chem. 2017;24(27):3002-3009. https://doi.org/10.2174/0929867324666170516123206
  • Fabbro-Peray P, Zouaoui S, Darlix A, Fabbro M, Pallud J, Rigau V, Mathieu-Daude H, Bessaoud F, Bauchet F, Riondel A, Sorbets E, Charissoux M, Amelot A, Mandonnet E, Figarella-Branger D, Duffau H, Tretarre B, Taillandier L, Bauchet L. Association of patterns of care, prognostic factors, and use of radiotherapy-temozolomide therapy with survival in patients with newly diagnosed glioblastoma: A French national population-based study. J Neurooncol. 2019 Mar;142(1):91-101. https://doi.org/10.1007/s11060-018-03065-z
  • Rajaratnam V, Islam MM, Yang M, Slaby R, Ramirez HM, Mirza SP. Glioblastoma: Pathogenesis and Current Status of Chemotherapy and Other Novel Treatments. Cancers (Basel). 2020 Apr 10;12(4):937. https://doi.org/10.3390/cancers12040937
  • Wesolowski JR, Rajdev P, Mukherji SK. Temozolomide (Temodar). AJNR Am J Neuroradiol. 2010 Sep;31(8):1383-4. https://doi.org/10.3174/ajnr.A2170
  • Ansari U, Chen V, Sedighi R, Syed B, Muttalib Z, Ansari K, Ansari F, Nadora D, Razick D, Lui F. Role of the UNC13 family in human diseases: A literature review. AIMS Neurosci. 2023 Dec 6;10(4):388-400. https://doi.org/10.3934/Neuroscience.2023029
  • Dittman JS. Unc13: a multifunctional synaptic marvel. Curr Opin Neurobiol. 2019 Aug;57:17-25. https://doi.org/10.1016/j.conb.2018.12.011
  • Varoqueaux F, Sons MS, Plomp JJ, Brose N. Aberrant morphology and residual transmitter release at the Munc13-deficient mouse neuromuscular synapse. Mol Cell Biol. 2005 Jul;25(14):5973-84. https://doi.org/10.1128/MCB.25.14.5973-5984.2005
  • Willemse SW, Harley P, van Eijk RPA, Demaegd KC, Zelina P, Pasterkamp RJ, van Damme P, Ingre C, van Rheenen W, Veldink JH, Kiernan MC, Al-Chalabi A, van den Berg LH, Fratta P, van Es MA. UNC13A in amyotrophic lateral sclerosis: from genetic association to therapeutic target. J Neurol Neurosurg Psychiatry. 2023 Aug;94(8):649-656. https://doi.org/10.1136/jnnp-2022-330504
  • Aricò M, Boggio E, Cetica V, Melensi M, Orilieri E, Clemente N, Cappellano G, Buttini S, Soluri MF, Comi C, Dufour C, Pende D, Dianzani I, Ellis SR, Pagliano S, Marcenaro S, Ramenghi U, Chiocchetti A, Dianzani U. Variations of the UNC13D gene in patients with autoimmune lymphoproliferative syndrome. PLoS One. 2013 Jul 1;8(7):e68045. https://doi.org/10.1371/journal.pone.0068045
  • Zhang K, Jordan MB, Marsh RA, Johnson JA, Kissell D, Meller J, Villanueva J, Risma KA, Wei Q, Klein PS, Filipovich AH. Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH. Blood. 2011 Nov 24;118(22):5794-8. https://doi.org/10.1182/blood-2011-07-370148
  • Ariel P, Ryan TA. New insights into molecular players involved in neurotransmitter release. Physiology (Bethesda). 2012 Feb;27(1):15-24. https://doi.org/10.1152/physiol.00035.2011
  • Dong W, Zhao L, Zhang S, Zhang S, Si H. Circ-KIAA0907 inhibits the progression of oral squamous cell carcinoma by regulating the miR-96-5p/UNC13C axis. World J Surg Oncol. 2021 Mar 14;19(1):75. https://doi.org/10.1186/s12957-021-02184-8
  • Kumar VB, Lee CH, Su TC, Lin CC, Mohammedsaleh ZM, Yeh CM, Kiefer R, Lin SH. Prognostic and Clinical Implications of UNC13C expression in Hepatocellular Carcinoma Patients. Int J Med Sci. 2023 Aug 6;20(9):1235-1239. https://doi.org/10.7150/ijms.80488
  • Gulluoglu S, Tuysuz EC, Sahin M, Kuskucu A, Kaan Yaltirik C, Ture U, Kucukkaraduman B, Akbar MW, Gure AO, Bayrak OF, Dalan AB. Simultaneous miRNA and mRNA transcriptome profiling of glioblastoma samples reveals a novel set of OncomiR candidates and their target genes. Brain Res. 2018 Dec 1;1700:199-210. https://doi.org/10.1016/j.brainres.2018.08.035
  • Miller HE, Bishop AJR. Correlation AnalyzeR: functional predictions from gene co-expression correlations. BMC Bioinformatics. 2021 Apr 20;22(1):206. https://doi.org/10.1186/s12859-021-04130-7
  • Chandrashekar DS, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M, Netto GJ, Qin ZS, Kumar S, Manne U, Creighton CJ, Varambally S. UALCAN: An update to the integrated cancer data analysis platform. Neoplasia. 2022 Mar;25:18-27. https://doi.org/10.1016/j.neo.2022.01.001
  • Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017 Jul 3;45(W1):W98-W102. https://doi.org/10.1093/nar/gkx247
  • Augustin I, Korte S, Rickmann M, Kretzschmar HA, Südhof TC, Herms JW, Brose N. The cerebellum-specific Munc13 isoform Munc13-3 regulates cerebellar synaptic transmission and motor learning in mice. J Neurosci. 2001 Jan 1;21(1):10-7. https://doi.org/10.1523/JNEUROSCI.21-01-00010.2001
  • Meunier FA, Hu Z. Functional Roles of UNC-13/Munc13 and UNC-18/Munc18 in Neurotransmission. Adv Neurobiol. 2023;33:203-231. https://doi.org/10.1007/978-3-031-34229-5_8
  • Batiuk MY, Martirosyan A, Wahis J, de Vin F, Marneffe C, Kusserow C, Koeppen J, Viana JF, Oliveira JF, Voet T, Ponting CP, Belgard TG, Holt MG. Identification of region-specific astrocyte subtypes at single cell resolution. Nat Commun. 2020 Mar 5;11(1):1220. https://doi.org/10.1038/s41467-019-14198-8
  • Wang YY, Liu SC, Yang Z, Zhang T. Impaired hippocampal synaptic plasticity in C6 glioma-bearing rats. J Neurooncol. 2011 Jul;103(3):469-77. https://doi.org/10.1007/s11060-010-0447-7
  • Janabi N, Peudenier S, Héron B, Ng KH, Tardieu M. Establishment of human microglial cell lines after transfection of primary cultures of embryonic microglial cells with the SV40 large T antigen. Neurosci Lett. 1995 Aug 4;195(2):105-8. https://doi.org/10.1016/0304-3940(94)11792-h
There are 22 citations in total.

Details

Primary Language English
Subjects Cancer Cell Biology
Journal Section Articles
Authors

Didem Seven 0000-0003-3406-5905

Altay Burak Dalan 0000-0002-5644-5725

Ömer Faruk Bayrak 0000-0001-7562-6604

Early Pub Date March 23, 2025
Publication Date
Submission Date October 25, 2024
Acceptance Date November 25, 2024
Published in Issue Year 2025 Volume: 15 Issue: 1

Cite

APA Seven, D., Dalan, A. B., & Bayrak, Ö. F. (2025). Unveiling the Expression of UNC13C in Brain and Glioblastoma Cells. Clinical and Experimental Health Sciences, 15(1), 198-202. https://doi.org/10.33808/clinexphealthsci.1573250
AMA Seven D, Dalan AB, Bayrak ÖF. Unveiling the Expression of UNC13C in Brain and Glioblastoma Cells. Clinical and Experimental Health Sciences. March 2025;15(1):198-202. doi:10.33808/clinexphealthsci.1573250
Chicago Seven, Didem, Altay Burak Dalan, and Ömer Faruk Bayrak. “Unveiling the Expression of UNC13C in Brain and Glioblastoma Cells”. Clinical and Experimental Health Sciences 15, no. 1 (March 2025): 198-202. https://doi.org/10.33808/clinexphealthsci.1573250.
EndNote Seven D, Dalan AB, Bayrak ÖF (March 1, 2025) Unveiling the Expression of UNC13C in Brain and Glioblastoma Cells. Clinical and Experimental Health Sciences 15 1 198–202.
IEEE D. Seven, A. B. Dalan, and Ö. F. Bayrak, “Unveiling the Expression of UNC13C in Brain and Glioblastoma Cells”, Clinical and Experimental Health Sciences, vol. 15, no. 1, pp. 198–202, 2025, doi: 10.33808/clinexphealthsci.1573250.
ISNAD Seven, Didem et al. “Unveiling the Expression of UNC13C in Brain and Glioblastoma Cells”. Clinical and Experimental Health Sciences 15/1 (March 2025), 198-202. https://doi.org/10.33808/clinexphealthsci.1573250.
JAMA Seven D, Dalan AB, Bayrak ÖF. Unveiling the Expression of UNC13C in Brain and Glioblastoma Cells. Clinical and Experimental Health Sciences. 2025;15:198–202.
MLA Seven, Didem et al. “Unveiling the Expression of UNC13C in Brain and Glioblastoma Cells”. Clinical and Experimental Health Sciences, vol. 15, no. 1, 2025, pp. 198-02, doi:10.33808/clinexphealthsci.1573250.
Vancouver Seven D, Dalan AB, Bayrak ÖF. Unveiling the Expression of UNC13C in Brain and Glioblastoma Cells. Clinical and Experimental Health Sciences. 2025;15(1):198-202.

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