JPMA. The Journal of the Pakistan Medical Association · 2026
Transcriptomic Analysis Identifies the PVT1-miR-34a Axis as a Novel Non-Coding RNA Therapeutic Target in Diffuse Intrinsic Pontine Glioma.
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Farooq Ayesha, Haroon Hurmat, Khan Faisal
Аннотация
OBJECTIVES: Diffuse intrinsic pontine glioma (DIPG) is a lethal paediatric brainstem tumour with a median survival under one year and no effective therapy. Although non-coding RNAs (ncRNAs) regulate tumour progression, their regulatory networks in DIPG remain poorly characterised. This study aimed to identify dysregulated lncRNA- miRNA-mRNA axes in DIPG through integrated transcriptomic analysis, computationally validate these networks, and investigate their downstream impact on cancer-related pathways to reveal novel therapeutic targets for RNAbased precision medicine.
METHOD: This study was conducted at the Precision Medicine Lab, National Centre in Big Data and Cloud Computing (NCBC), Peshawar, from 1st July to 22nd August 2025. RNA-seq datasets comprising 25 DIPG and 45 normal brain samples were obtained from GEO. Following normalization and differential expression analysis (padj < 0.05, |log2FC| > 2), dysregulated lncRNAs, miRNAs, and mRNAs were integrated into a ceRNA network using LncBase and miRTarBase. KEGG pathway enrichment, STRING protein-protein interaction analysis, Cytoscape network visualization, and Spearman correlation analysis were performed to identify and validate functionally relevant regulatory interactions.
RESULTS: PCA demonstrated clear separation between DIPG and control transcriptomes. PVT1 was significantly upregulated (log2FC = 3.44), whereas miR-34a was downregulated (log2FC = -3.66). Eleven oncogenic mRNAs, including NOTCH1, PDGFRA, CDK4, SOX2, and MYC, were identified as predicted targets and formed a highly connected STRING interaction network. KEGG enrichment highlighted "MicroRNAs in cancer," while correlation analysis supported an inverse PVT1-miR-34a relationship and positive associations with these oncogenes, consistent with a ceRNA regulatory mechanism.
CONCLUSIONS: The PVT1-miR-34a axis appears to promote oncogenic pathways in DIPG. Targetting PVT1 or restoring miR-34a may represent potential RNA-based therapeutic strategies, warranting further experimental validation through reporter and knockdown assays.
METHOD: This study was conducted at the Precision Medicine Lab, National Centre in Big Data and Cloud Computing (NCBC), Peshawar, from 1st July to 22nd August 2025. RNA-seq datasets comprising 25 DIPG and 45 normal brain samples were obtained from GEO. Following normalization and differential expression analysis (padj < 0.05, |log2FC| > 2), dysregulated lncRNAs, miRNAs, and mRNAs were integrated into a ceRNA network using LncBase and miRTarBase. KEGG pathway enrichment, STRING protein-protein interaction analysis, Cytoscape network visualization, and Spearman correlation analysis were performed to identify and validate functionally relevant regulatory interactions.
RESULTS: PCA demonstrated clear separation between DIPG and control transcriptomes. PVT1 was significantly upregulated (log2FC = 3.44), whereas miR-34a was downregulated (log2FC = -3.66). Eleven oncogenic mRNAs, including NOTCH1, PDGFRA, CDK4, SOX2, and MYC, were identified as predicted targets and formed a highly connected STRING interaction network. KEGG enrichment highlighted "MicroRNAs in cancer," while correlation analysis supported an inverse PVT1-miR-34a relationship and positive associations with these oncogenes, consistent with a ceRNA regulatory mechanism.
CONCLUSIONS: The PVT1-miR-34a axis appears to promote oncogenic pathways in DIPG. Targetting PVT1 or restoring miR-34a may represent potential RNA-based therapeutic strategies, warranting further experimental validation through reporter and knockdown assays.