Non-coding RNAs (ncRNAs) and multidrug resistance in glioblastoma: Therapeutic challenges and opportunities

Non-coding RNAs (ncRNAs) have been recognized as pivotal regulators of transcriptional and post-transcriptional gene modulation, exerting a profound influence on a diverse array of biological and pathological cascades, including the intricate mechanisms underlying tumorigenesis and the acquisition of drug resistance in neoplastic cells. Glioblastoma (GBM), recognized as the foremost and most aggressive neoplasm originating in the brain, is distinguished by its formidable resistance to the cytotoxic effects of chemotherapeutic agents and ionizing radiation. Recent years have witnessed an escalating interest in comprehending the involvement of ncRNAs, particularly lncRNAs, in GBM chemoresistance. LncRNAs, a subclass of ncRNAs, have been demonstrated as dynamic modulators of gene expression at the epigenetic, transcriptional, and post-transcriptional levels. Disruption in the regulation of lncRNAs has been observed across various human malignancies, including GBM, and has been linked with developing multidrug resistance (MDR) against standard chemotherapeutic agents. The potential of targeting specific ncRNAs or their downstream effectors to surmount chemoresistance is also critically evaluated, specifically focusing on ongoing preclinical and clinical investigations exploring ncRNA-based therapeutic strategies for glioblastoma. Nonetheless, targeting lncRNAs for therapeutic objectives presents hurdles, including overcoming the blood-brain barrier and the brief lifespan of oligonucleotide RNA molecules. Understanding the complex relationship between ncRNAs and the chemoresistance characteristic in glioblastoma provides valuable insights into the fundamental molecular mechanisms. It opens the path for the progression of innovative and effective therapeutic approaches to counter the therapeutic challenges posed by this aggressive brain tumor. This comprehensive review highlights the complex functions of diverse ncRNAs, including miRNAs, circRNAs, and lncRNAs, in mediating glioblastoma's chemoresistance.