Transcriptomic Meta-Analysis and Functional Validation Identify Long Non-Coding RNAs as Modulators of Zika Virus-Mediated Oncolysis in Glioblastoma Multiforme Cell Lines
Abstract
Glioblastoma multiforme (GBM) is the most aggressive primary brain malignancy with limited treatment options and poor clinical outcomes. There is growing interest in using Zika virus as a treatment for GBM due to its selectivity in finding and killing rapidly proliferating neural cells. Several studies reproducibly show that Zika can effectively kill GBM cells. We sought to uncover the molecular mechanisms driving this cytotoxic effect by performing a meta-analysis of transcriptomic studies in which Zika virus was used to kill GBM cells. We integrated four datasets from studies on GBM and added neuroblastoma (NBM) studies as an outgroup comparator. Our analysis identified a shared molecular signature of the Zika-infected GBM cell. Interestingly, GBM cells killed by the Zika virus showed dysregulation of pathways commonly implicated in proliferation and metastasis, including TNF, NF-κB, and p53 signaling. Using a hypothesis-free design, we found several long non-coding RNAs (lncRNAs) that were consistently dysregulated in Zika-infected GBMs, many of which have previously unrecognized roles in cancer cell death. Among this group, we validated four lncRNAs for a role in Zika-mediated oncolysis. We functionally tested MELTF-AS1, TIPARP-AS1, NR2F1-AS1, and SLC9A3-AS1 in adult GBM cell lines using siRNA-mediated knockdown. Silencing of MELTF-AS1 augmented Zika-induced cell death, while knockdown of TIPARP-AS1, NR2F1-AS1, and SLC9A3-AS1 attenuated oncolysis, identifying lncRNAs…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in cell cultures (in vitro), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- Regulation of nucleolus assembly by non-coding RNA polymerase II transcripts
- For a Healthy Histone Code, a Little SUMO in the Tail Keeps the Acetyl Away
- Discovering a binary CTCF code with a little help from BORIS
- Article Commentary: Stabilizing the Code–-Methods to Preserve RNA Prove Their Worth
- Foreword to the Special Issue for the RINTC (The Implicit Seismic Risk of Code-Conforming Structures) Project
- Commentary: Promoting Health and Well-being in Pediatric Primary Care Settings: Using Health and Behavior Codes at Routine Well-child Visits
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.