• Unveiling the H19/miR-107/miR-133/BCL2L2 Axis: A Novel Regulatory Network Driving Glioblastoma Progression
  • Mohammad Javad Mokhtari,1,* Zahra Salah,2 Fatemeh Dehghan,3
    1. Department of Biology, Zarg.C., Islamic Azad University, Zarghan, Iran
    2. Department of Biology, Zarg.C., Islamic Azad University, Zarghan, Iran
    3. Department of Biology, Zarg.C., Islamic Azad University, Zarghan, Iran


  • Introduction: Glioblastoma (GBM) represents the most aggressive from of primary brain neoplasm, characterized by a dismal prognosis despite the implementation of current therapeutic modalities. The anti-apoptotic gene BCL2L2 has been implicated in the progression of the long non-coding RNA H19 has emerged as a pivotal regulator in oncogenesis, exerting its influence on gene expression via interactions with microRNAs. The present study seeks to elucidate the regulatory interplay between H19 and BCL2L2, mediated by shared miRNAs, to identify a novel therapeutic axis capable of modulating apoptotic pathways and enhancing clinical outcomes in GBM management.
  • Methods: Expression profiles of H19 and BCL2L2 in GBM were analyzed using the GEPIA2 (http://gepia2.cancer-pku.cn/#index) database. Potential miRNAs targeting both H19 and BCL2L2 were identified through the ENCORI ( https://rnasysu.com/encori/ ) database. Interaction networks were constructed and visualized using the RStudio package to explore regulatory relationships between lncRNAs , miRNAs, and target genes.
  • Results: Bioinformatic analysis identified several miRNAs with potential interactions involving the long non-coding RNA H19 and the anti-apoptotic gene BCL2L2. Notably, miR-107, miR-335, miR-491-5p, miR-103a-3p, and miR-106a-5p were among the candidates, with miR-107 and miR-133 highlighted due to their well-established roles in regulating GBM progression. H19 appears to function as a competing endogenous RNA (ceRNA), sequestering these miRNAs and thereby mitigating their suppressive effects on BCL2L2 expression. This molecular derepression of BCL2L2 contributes to enhanced cellular survival, increased invasive capacity, elevated stemness characteristics, and resistance to chemotherapeutic agents such as temozolomide. At the mechanistic level, upregulation of H19 maintains BCL2L2 expression, inhibits apoptotic pathways, and facilitates the advancement of GMB pathology.
  • Conclusion: The H19/miR-107/miR-133/BCL2L2 regulatory axis represents a critical pathway driving GBM aggressiveness. Targeting this axis could provide a promising therapeutic approach to limit tumor growth, invasion, and chemoresistance. We propose that this regulatory network be further validated in-vivo to confirm the functional interactions between H19, miR-107, miR-133, and BCL2L2 in this cancer.
  • Keywords: LncRNA, H19, Bcl2l2, GBM, Bioinformatics, MicroRNA