Synthetic miR-21 decoy circularized by tRNA splicing mechanism inhibited tumorigenesis in glioblastoma in vitro and in vivo models
| Autor: | Hadi Bayat, Mohammad Hossein Pourgholami, Saeid Rahmani, Safura Pournajaf, Seyed Javad Mowla |
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| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Molecular Therapy: Nucleic Acids, Vol 32, Iss , Pp 432-444 (2023) |
| Druh dokumentu: | article |
| ISSN: | 2162-2531 52484491 |
| DOI: | 10.1016/j.omtn.2023.04.001 |
| Popis: | Glioblastoma multiforme (GBM) is the deadliest primary central nervous system tumor. miRNAs (miRs), a class of non-coding RNAs, are considered pivotal post-transcriptional regulators of cell signaling pathways. miR-21 is a reliable oncogene that promotes tumorigenesis of cancer cells. We first performed an in silico analysis on 10 microarray datasets retrieved from TCGA and GEO databases to elucidate top differentially expressed miRs. Furthermore, we generated a circular miR-21 decoy, CM21D, using the tRNA-splicing mechanism in GBM cell models, U87 and C6. The inhibitory efficacy of CM21D with that of a linear form, LM21D, was compared under in vitro conditions and an intracranial C6 rat glioblastoma model. miR-21 significantly overexpressed in GBM samples and confirmed in GBM cell models using qRT-PCR. CM21D was more efficient than LM21D at inducing apoptosis, inhibiting cell proliferation and migration, and interrupting the cell cycle by restoring the expression of miR-21 target genes at RNA and protein levels. Moreover, CM21D suppressed tumor growth more effectively than LM21D in the C6-rat GBM model (p |
| Databáze: | Directory of Open Access Journals |
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