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Exploring the Role of Long Non-Coding RNAs in Mediating Cisplatin Resistance in Glioma/Glioblastoma Cells
Hadi Sahrai1, Reza Mosaddeghi-Heris2, Nasrin Forghani2
1Research Center for Evidence-Based Medicine, Iranian EBM Centre: A JBI Centre of Excellence, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz 5166614711, Iran.
Abstract:
Malignant gliomas are highly aggressive primary brain tumors for which the therapeutic efficacy of cisplatin is frequently limited by intrinsic or acquired drug resistance. Despite advances in adjuvant therapies, overcoming chemoresistance remains a major challenge in the treatment of these malignancies. Emerging evidence indicates that long non-coding RNAs (lncRNAs), a class of non-protein-coding transcripts involved in gene regulation, play important roles in modulating treatment responses. Several lncRNAs, including differentiation antagonizing non-protein-coding RNA (DANCR), HOXD antisense growth-associated long non-coding RNA (HOXD-AS1), MEG3, MALAT1, and HOTAIR, have been implicated in pathways associated with glioma progression and therapeutic resistance. In particular, DANCR has been reported to promote cisplatin resistance in glioma cells through suppression of apoptosis and activation of pro-survival signaling pathways. This review summarizes current evidence regarding the roles of lncRNAs in cisplatin resistance, highlighting mechanisms such as regulation of drug transport, DNA damage repair, apoptosis, cancer stem-cell maintenance, and signaling pathways associated with treatment adaptation. We also discuss current limitations, challenges for clinical translation, and gaps in the existing evidence. A better understanding of lncRNA-mediated resistance mechanisms may facilitate the identification of novel therapeutic targets and inform future studies aimed at overcoming cisplatin resistance in malignant gliomas.
Insights
Long non-coding RNAs (lncRNAs) contribute to cisplatin resistance in malignant gliomas by affecting apoptosis and survival pathways. Understanding lncRNA roles may reveal new therapeutic targets for overcoming chemoresistance in brain tumors.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genomics
Background:
- Malignant gliomas are aggressive brain tumors with limited treatment options.
- Cisplatin efficacy is often hindered by drug resistance, a major therapeutic challenge.
- Long non-coding RNAs (lncRNAs) are emerging regulators of gene expression and treatment response.
Purpose of the Study:
- To review the current evidence on the role of lncRNAs in cisplatin resistance in malignant gliomas.
- To highlight the molecular mechanisms by which lncRNAs mediate chemoresistance.
- To discuss challenges and future directions for clinical translation.
Main Methods:
- Literature review of studies investigating lncRNAs and cisplatin resistance in gliomas.
- Analysis of lncRNA functions including gene regulation, apoptosis, and signaling pathways.
- Synthesis of evidence on specific lncRNAs like DANCR, HOXD-AS1, MEG3, MALAT1, and HOTAIR.
Main Results:
- Several lncRNAs are implicated in glioma progression and therapeutic resistance.
- lncRNAs modulate cisplatin resistance through mechanisms like drug transport, DNA repair, and apoptosis regulation.
- Differentiation antagonizing non-protein-coding RNA (DANCR) promotes cisplatin resistance by suppressing apoptosis and activating pro-survival pathways.
Conclusions:
- lncRNAs play a significant role in the development of cisplatin resistance in malignant gliomas.
- Targeting lncRNAs offers potential for novel therapeutic strategies to overcome chemoresistance.
- Further research is needed to address limitations and facilitate clinical translation of lncRNA-based therapies.
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