Role of long noncoding RNAs in temozolomide-resistant glioblastoma

Abstract Chemoresistance is considered as one of the major obstacles in the postgenomic era of cancer treatment. Recent studies envisaged the crucial regulatory role of long noncoding RNA (lncRNA)/microRNA (miRNA) and their interaction in cancer chemotherapy and personalized medicine. Glioblastoma (GBM) is one of the devastating brain cancers and is highly malignant and resistant to therapy. LncRNAs are long noncoding RNAs with nucleotide length of more than 200 bp, lack protein-coding potential, and were found to regulate cellular processes such as chromatin epigenetics, posttranscriptional mRNA processing, gene regulation, glioma cancer stem cell (GCSC) self-renewal, drug metabolism, and chemoresistance. In GBM, the survival period of most of the patients is less than 15 months. The most common drug utilized for treating GBM is temozolomide as a part of first-line therapy. Resistance to temozolomide results in tumor recurrence, epithelial to mesenchymal transition (EMT), and therapy failure. This chapter describes how various lncRNAs contribute to drug resistance to temozolomide in GBM patients and interaction of lncRNA with miRNAs, modulation of chromatin epigenetics by lncRNA, the role of RNA modifications such as m6A and m5C in mRNA in GBM cancer progression and TMZ-drug resistance.