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Targeting miR?155?5p and miR?221?3p by peptide nucleic acids induces caspase?3 activation and apoptosis in temozolomide?resistant T98G glioma cells.

ABSTRACT: The present study investigated the effects of the combined treatment of two peptide nucleic acids (PNAs), directed against microRNAs involved in caspase?3 mRNA regulation (miR?155?5p and miR?221?3p) in the temozolomide (TMZ)?resistant T98G glioma cell line. These PNAs were conjugated with an octaarginine tail in order to obtain an efficient delivery to treated cells. The effects of singularly administered PNAs or a combined treatment with both PNAs were examined on apoptosis, with the aim to determine whether reversion of the drug?resistance phenotype was obtained. Specificity of the PNA?mediated effects was analyzed by reverse transcription?quantitative polymerase?chain reaction, which demonstrated that the effects of R8?PNA?a155 and R8-PNA-a221 anti?miR PNAs were specific. Furthermore, the results obtained confirmed that both PNAs induced apoptosis when used on the temozolomide?resistant T98G glioma cell line. Notably, co?administration of both anti?miR?155 and anti?miR?221 PNAs was associated with an increased proapoptotic activity. In addition, TMZ further increased the induction of apoptosis in T98G cells co?treated with anti?miR?155 and anti?miR?221 PNAs.

SUBMITTER: Milani R

PROVIDER: S-EPMC6561624 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Targeting miR‑155‑5p and miR‑221‑3p by peptide nucleic acids induces caspase‑3 activation and apoptosis in temozolomide‑resistant T98G glioma cells.

Milani Roberta R Brognara Eleonora E Fabbri Enrica E Manicardi Alex A Corradini Roberto R Finotti Alessia A Gasparello Jessica J Borgatti Monica M Cosenza Lucia Carmela LC Lampronti Ilaria I Dechecchi Maria Cristina MC Cabrini Giulio G Gambari Roberto R

International journal of oncology 20190523 1

The present study investigated the effects of the combined treatment of two peptide nucleic acids (PNAs), directed against microRNAs involved in caspase‑3 mRNA regulation (miR‑155‑5p and miR‑221‑3p) in the temozolomide (TMZ)‑resistant T98G glioma cell line. These PNAs were conjugated with an octaarginine tail in order to obtain an efficient delivery to treated cells. The effects of singularly administered PNAs or a combined treatment with both PNAs were examined on apoptosis, with the aim to det ...[more]

PMID: 31180529

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Project description:BackgroundThe differentiation of stem cells from exfoliated deciduous teeth (SHEDs) into odontoblasts determines the regeneration of dentin-pulp complex. Non-coding RNAs (ncRNAs), including microRNA (miRNA) and long non-coding RNA (lncRNA), participate in many multiple biological processes, but the specific miRNAs involved in odontogenesis are incompletely defined. It was confirmed that lncRNA IGFBP7-AS1 could positively regulate odontogenetic differentiation in SHEDs. To investigate the downstream mechanisms of this process, miR-335-3p and miR-155-5p were found to be closely related with SHED odontogenic differentiation through whole-genome sequencing. The aim of the current study was to determine the role of miR-335-3p/miR-155-5p in IGFBP7-AS1-enhanced SHED differentiation and explore the potential mechanism of IGFBP7-AS1-mediated odontogenesis.MethodsPutative miR-335-3p/miR-155-5p binding sites within IGFBP7-AS1 were identified by bioinformatics analysis, and the binding of miR-335-3p/miR-155-5p to these sites was confirmed by dual-luciferase reporter gene assays. The effects of miR-335-3p/miR-155-5p in odontogenesis were detected by tissue nonspecific alkaline phosphatase staining, Alizarin red staining, quantitative real-time polymerase chain reaction (qRT-PCR) analyses, and western blot testing. The molecular mechanisms of miR-335-3p/miR-155-5p involved in IGFBP7-AS1-mediated odontogenesis were analysed by qRT-PCR and western blot testing.ResultsDual-luciferase reporter gene assays showed that miR-335-3p/miR-155-5p could directly bind to IGFBP7-AS1. MiR-335-3p and miR-155-5p both could down-regulate dentin sialophosphoprotein expression, and both miRNAs could inhibit IGFBP7-AS1-mediated SHED odontogenetic differentiation via suppression of the extracellular signal-regulated kinase (ERK) pathway.ConclusionsBoth miR-335-3p and miR-155-5p were negative regulators to IGFBP7-AS1-enhanced odontogenic differentiation of SHED through suppression of the ERK pathway.

Dataset Information

Targeting miR?155?5p and miR?221?3p by peptide nucleic acids induces caspase?3 activation and apoptosis in temozolomide?resistant T98G glioma cells.

Publications

Targeting miR‑155‑5p and miR‑221‑3p by peptide nucleic acids induces caspase‑3 activation and apoptosis in temozolomide‑resistant T98G glioma cells.

Similar Datasets

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