Effects of HSV-G47Δ Oncolytic Virus on Telomerase and Telomere Length Alterations in Glioblastoma Multiforme Cancer Stem Cells Under Hypoxia and Normoxia Conditions-Reference-Cited by-同舟云学术

Effects of HSV-G47Δ Oncolytic Virus on Telomerase and Telomere Length Alterations in Glioblastoma Multiforme Cancer Stem Cells Under Hypoxia and Normoxia Conditions

Published:2024-12 Issue:12 Volume:24 Page:1262-1274
ISSN:1568-0096
Container-title:Current Cancer Drug Targets
language:en
Short-container-title:CCDT

Author:

Vazifehmand Reza¹,Saeed Ali Dhuha²,Monem Homaie Foroozandeh³,Molaei Jalalvand Fatemeh⁴,Othman Zulkefley⁵,Deming Chau⁶,Stanslas Johnson⁷,Sekawi Zamberi¹

Affiliation:

1. Department of Medical Microbiology & Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor Darul Ehsan, Malaysia

2. Halal Products Research Institute, Universiti Putra Malaysia, 43400, UPM Serdang, Selangor, Malaysia

3. Departments of Biochemistry, Science and Research University- Fars Branch, Shiraz, Iran

4. Department of Microbiology, Lahijan Branch, Islamic Azad University, Lahijan, Iran

5. Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor Darul Ehsan, Malaysia

6. Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor Darul Ehsan, Malaysia;

7. Pharmacotherapeutics Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, UPM Serdang, Selangor, Malaysia

Abstract

Background: Due to the existence of tumor stem cells with tumorigenicity properties and resistance patterns, treatment of glioblastoma is not easy. Hypoxia is a major concern in glioblastoma therapy. Telomerase activity and telomere length alterations have been known to play a critical role in glioblastoma progression and invasion. Objective: This study aimed to investigate the effects of HSV-G47Δ oncolytic virus on telomerase and telomere length alterations in U251GBMCSCs (U251-Glioblastoma cancer stem cells) under hypoxia and normoxia conditions. Methods: U251-CSCs were exposed to the HSV-G47Δ virus in optimized MOI (Multiplicity of infection= 1/14 hours). An absolute telomere length and gene expression of telomerase subunits were determined using an absolute human telomere length quantification PCR assay. Furthermore, a bioinformatics pathway analysis was carried out to evaluate physical and genetic interactions between dysregulated genes with other potential genes and pathways. Results: Data revealed that U251CSCs had longer telomeres when exposed to HSV-G47Δ in normoxic conditions but had significantly shorter telomeres in hypoxic conditions. Furthermore, hTERC, DKC1, and TEP1 genes were significantly dysregulated in hypoxic and normoxic microenvironments. The analysis revealed that the expression of TERF2 was significantly reduced in both microenvironments, and two critical genes from the MRN complex, MER11 and RAD50, were significantly upregulated in normoxic conditions. RAD50 showed a significant downregulation pattern in the hypoxic niche. Our results suggested that repair complex in the telomeric structure could be targeted by HSV-G47Δ in both microenvironments. Conclusion: In the glioblastoma treatment strategy, telomerase and telomere complex could be potential targets for HSV-G47Δ in both microenvironments. conclusion: In glioblastoma treatment strategy, telomerase and telomere complex could be potential targets for HSV-G47∆ in both microenvironments.

Publisher

Bentham Science Publishers Ltd.