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Article Dans Une Revue Cancers Année : 2020

Temozolomide-Induced RNA Interactome Uncovers Novel LncRNA Regulatory Loops in Glioblastoma

Résumé

Resistance to chemotherapy by temozolomide (TMZ) is a major cause of glioblastoma (GBM) recurrence. So far, attempts to characterize factors that contribute to TMZ sensitivity have largely focused on protein-coding genes, and failed to provide effective therapeutic targets. Long noncoding RNAs (lncRNAs) are essential regulators of epigenetic-driven cell diversification, yet, their contribution to the transcriptional response to drugs is less understood. Here, we performed RNA-seq and small RNA-seq to provide a comprehensive map of transcriptome regulation upon TMZ in patient-derived GBM stem-like cells displaying different drug sensitivity. In a search for regulatory mechanisms, we integrated thousands of molecular associations stored in public databases to generate a background "RNA interactome". Our systems-level analysis uncovered a coordinated program of TMZ response reflected by regulatory circuits that involve transcription factors, mRNAs, miRNAs, and lncRNAs. We discovered 22 lncRNAs involved in regulatory loops and/or with functional relevance in drug response and prognostic value in gliomas. Thus, the investigation of TMZ-induced gene networks highlights novel RNA-based predictors of chemosensitivity in GBM. The computational modeling used to identify regulatory circuits underlying drug response and prioritizing gene candidates for functional validation is applicable to other datasets.
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Dates et versions

hal-03669755 , version 1 (16-05-2022)

Identifiants

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Sabrina Fritah, Arnaud Muller, Wei Jiang, Ramkrishna Mitra, Mohamed Sarmini, et al.. Temozolomide-Induced RNA Interactome Uncovers Novel LncRNA Regulatory Loops in Glioblastoma. Cancers, 2020, 12 (9), pp.2583. ⟨10.3390/cancers12092583⟩. ⟨hal-03669755⟩
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