Affiliation:
1. Department of Biochemical Engineering and Biotechnology Indian Institute of Technology Delhi New Delhi India
2. Centralized Core Research Facility All India Institute of Medical Sciences New Delhi India
3. Institute of Human Genetics University Hospital Düsseldorf, Heinrich‐Heine‐Universität Düsseldorf Germany
4. Department of Pathology All India Institute of Medical Sciences New Delhi India
Abstract
AbstractRecent studies have shed light on disrupted collagen signaling in Gliomas, yet the regulatory landscape remains largely unexplored. This study enquired into the role of polycomb repressive complex‐2 (PRC2)‐mediated H3K27me3 modification, a key epigenetic factor in glioma. Using in‐house data, we identified miRNAs downregulated in glioblastoma (GBM) with the potential to regulate Collagen VI family genes. Notably, miR‐3189 emerged as a prime PRC2 target. Its expression was significantly downregulated in Indian GBM patients as well as other glioma cohorts. Mechanistic insights, involving Luciferase assays, mutagenesis, and Western blot analysis, confirmed direct targeting of Collagen VI member COL6A2 by miR‐3189‐3p. Functional assays demonstrated that miR‐3189‐3p restrained GBM malignancy by inhibiting proliferation, migration, and epithelial–mesenchymal transition (EMT). Conversely, COL6A2 overexpressed in GBM patients, countered miR‐3189, and promoted the malignant phenotype. Gene set enrichment analysis highlighted EMT enrichment in GBM patients with elevated COL6A2 expression, carrying prognostic implications. This study uncovers intricate interactions between two epigenetic regulators—H3K27me3 and miR‐3189—working synergistically to modulate Collagen VI gene; thus, influencing the malignancy of GBM. Targeting this H3K27me3|miR‐3189‐3p|COL6A2 axis presents a potential therapeutic avenue against GBM.