Long non-coding RNA in glioma: novel genetic players in temozolomide resistance

Glioma is the most common primary malignant brain tumor in adults and accounts for approximately 80% of brain and central nervous system tumors. In 2021, the World Health Organization (WHO) published a new taxonomy for glioma based on its histological features and molecular alterations. Isocitrate dehydrogenase (IDH) catalyzes the decarboxylation of isocitrate, a critical metabolic reaction in energy generation in cells. Mutations in the IDH genes interrupt cell differentiation and serve as molecular biomarkers that can be used to classify gliomas. For example, the mutant IDH is widely detected in low-grade gliomas, whereas the wild type is in high-grade ones, including glioblastomas. Long non-coding RNAs (lncRNAs) are epigenetically involved in gene expression and contribute to glioma development. To investigate the potential use of lncRNAs as biomarkers, we examined lncRNA dysregulation dependent on the IDH mutation status. We found that several lncRNAs, namely, AL606760.2, H19, MALAT1, PVT1 and SBF2-AS1 may function as glioma risk factors, whereas AC068643.1, AC079228.1, DGCR5, FAM13A-AS1, HAR1A and WDFY3-AS2 may have protective effects. Notably, H19, MALAT1, PVT1, and SBF2-AS1 have been associated with temozolomide resistance in glioma patients. This review study suggests that targeting glioma-associated lncRNAs might aid the treatment of glioma.