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Published on: October 4, 2019
Arsenic trioxide Alters the MicroRNA Expression Profile of U87 glioblastoma
Fatemeh Shidfar, Seyed H Ghaffari1, Gholamreza Tavoosidana
1Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. shghaffari200@yahoo.com.
Abstract:
MicroRNAs (miRNAs) have a major role in cancer pathogenesis, cells growth and apoptosis. We studied the dysregulation of miRNAs after the induction of apoptosis by 4 μM dose of ATO in glioblastoma cell line, U87. The anticancer effect of ATO was verified using MTT, BrdU cell proliferation assay and flow cytometric analysis. Differential expressions of 88 cancer-related miRNAs were analyzed by real-time reverse transcription PCR using miRNA PCR cancer-array system. The fold changes of miRNAs were calculated by comparing the results of treated to untreated control. Among the 88 cancer-related miRNAs, 2-fold upregulation was detected in 26 miRNAs and downregulation in 10 miRNAs compared to the control. The role of some of the miRNAs with significant changes was investigated by searching the literature and studying their roles in apoptosis, cell cycle and in various cellular signalling pathways. Our results showed that ATO modified the expression of a significant number of cancer-related miRNAs in glioblastoma cell line; most of these especially the upregulated miRNAs, were known as tumor suppressors with extensive roles in cancer associated processes and pathways. This study supports the mediatory role of miRNAs in anticancer effect of ATO.
Insights
Arsenic trioxide (ATO) alters microRNA (miRNA) expression in glioblastoma cells, inducing apoptosis. Upregulated tumor suppressor miRNAs suggest a key role for miRNAs in ATO's anticancer effects.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are crucial regulators in cancer development, influencing cell growth and apoptosis.
- Glioblastoma is an aggressive brain tumor with limited treatment options.
- Arsenic trioxide (ATO) exhibits anticancer properties, but its molecular mechanisms, particularly miRNA involvement, require further elucidation.
Purpose of the Study:
- To investigate the impact of ATO on miRNA expression in U87 glioblastoma cells.
- To identify specific miRNAs dysregulated by ATO-induced apoptosis.
- To explore the potential role of these miRNAs in ATO's anti-cancer mechanism.
Main Methods:
- U87 glioblastoma cells were treated with 4 μM ATO to induce apoptosis.
- Anticancer effects were confirmed using MTT, BrdU proliferation assays, and flow cytometry.
- Differential expression of 88 cancer-related miRNAs was analyzed using real-time RT-PCR with a miRNA cancer array.
Main Results:
- ATO treatment significantly altered the expression of numerous cancer-related miRNAs in U87 cells.
- 26 miRNAs showed at least a 2-fold upregulation, while 10 miRNAs were downregulated compared to controls.
- Many upregulated miRNAs were identified as tumor suppressors involved in cancer-related pathways.
Conclusions:
- ATO modulates miRNA expression profiles in glioblastoma cells, contributing to its apoptotic effects.
- The dysregulation of tumor-suppressive miRNAs highlights their mediatory role in ATO's anti-cancer activity.
- This study provides insights into the molecular mechanisms underlying ATO's efficacy against glioblastoma.
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