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Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
The evaluation expression of non-coding RNAs in response to HSV-G47∆ oncolytic virus infection in glioblastoma
Reza Vazifehmand1, Dhuha Saeed Ali2, Zulkefley Othman3
1Department of Medical Microbiology & Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), Serdang, Selangor Darul Ehsan, 43400, Malaysia.
Abstract:
Glioblastoma multiforme is the most aggressive astrocytes brain tumor. Glioblastoma cancer stem cells and hypoxia conditions are well-known major obstacles in treatment. Studies have revealed that non-coding RNAs serve a critical role in glioblastoma progression, invasion, and resistance to chemo-radiotherapy. The present study examined the expression levels of microRNAs (in normoxic condition) and long non-coding RNAs (in normoxic and hypoxic conditions) in glioblastoma stem cells treated with the HSV-G47∆. The expression levels of 43 miRNAs and 8 lncRNAs isolated from U251-GBM-CSCs were analyzed using a miRCURY LNA custom PCR array and a quantitative PCR assay, respectively. The data revealed that out of 43 miRNAs that only were checked in normoxic condition, the only 8 miRNAs, including miR-7-1, miR-let-7b, miR-130a, miR-137, miR-200b, miR-221, miR-222, and miR-874, were markedly upregulated. The expression levels of lncRNAs, including LEF1 antisense RNA 1 (LEF1-AS1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), long intergenic non-protein coding RNA 470 (LINC00470), tumor suppressor candidate 7 (TUSC7), HOX transcript antisense RNA (HOTAIR), nuclear paraspeckle assembly transcript 1 (NEAT1), and X inactive specific transcript (XIST), were markedly downregulated in the hypoxic microenvironment, and H19-imprinted maternally expressed transcript (H19) was not observed to be dysregulated in this environment. Under normoxic conditions, LEF1-AS1, MALAT1, LINC00470, H19, HOTAIR, NEAT1, and XIST were downregulated and TUSC7 was not targeted by HSV-G47∆. Overall, the present data shows HSVG47Δ treatment deregulates non-coding RNA expression in GBM-CSC tumor microenvironments.
Insights
Treatment with HSV-G47Δ deregulates non-coding RNA expression in glioblastoma stem cells. This study identified specific microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) affected by this treatment under normoxic and hypoxic conditions.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with cancer stem cells and hypoxia posing treatment challenges.
- Non-coding RNAs (ncRNAs) play a crucial role in GBM progression, invasion, and therapeutic resistance.
Purpose of the Study:
- To investigate the expression levels of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in glioblastoma stem cells (GSCs) treated with HSV-G47Δ.
- To analyze ncRNA expression under both normoxic and hypoxic conditions.
Main Methods:
- Expression analysis of 43 miRNAs and 8 lncRNAs in U251-GBM-CSCs using miRCURY LNA custom PCR array and quantitative PCR.
- Experiments were conducted under both normoxic and hypoxic conditions following HSV-G47Δ treatment.
Main Results:
- Eight miRNAs (miR-7-1, let-7b, miR-130a, miR-137, miR-200b, miR-221, miR-222, miR-874) were upregulated in normoxic conditions.
- Under hypoxia, LEF1-AS1, MALAT1, LINC00470, TUSC7, HOTAIR, NEAT1, and XIST lncRNAs were downregulated; H19 was not dysregulated.
- Under normoxia, LEF1-AS1, MALAT1, LINC00470, H19, HOTAIR, NEAT1, and XIST were downregulated; TUSC7 was unaffected.
Conclusions:
- HSV-G47Δ treatment significantly alters the expression of specific miRNAs and lncRNAs in glioblastoma stem cell tumor microenvironments.
- The findings highlight the role of ncRNAs in GBM's response to oncolytic virus therapy and varying oxygen conditions.
