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MicroRNAs as the pivotal regulators of cisplatin resistance in osteosarcoma
1Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:
Osteosarcoma (OS) is an aggressive bone tumor that originates from mesenchymal cells. It is considered as the eighth most frequent childhood cancer that mainly affects the tibia and femur among the teenagers and young adults. OS can be usually diagnosed by a combination of MRI and surgical biopsy. The intra-arterial cisplatin (CDDP) and Adriamycin is one of the methods of choices for the OS treatment. CDDP induces tumor cell death by disturbing the DNA replication. Although, CDDP has a critical role in improving the clinical complication in OS patients, a high ratio of CDDP resistance is observed among these patients. Prolonged CDDP administrations have also serious side effects in normal tissues and organs. Therefore, the molecular mechanisms of CDDP resistance should be clarified to define the novel therapeutic modalities in OS. Multidrug resistance (MDR) can be caused by various cellular and molecular processes such as drug efflux, detoxification, and signaling pathways. MicroRNAs (miRNAs) are the key regulators of CDDP response by the post transcriptional regulation of target genes involved in MDR. In the present review we have discussed all of the miRNAs associated with CDDP response in OS cells. It was observed that the majority of reported miRNAs increased CDDP sensitivity in OS cells through the regulation of signaling pathways, apoptosis, transporters, and autophagy. This review highlights the miRNAs as reliable non-invasive markers for the prediction of CDDP response in OS patients.
Insights
MicroRNAs (miRNAs) can overcome cisplatin resistance in osteosarcoma (OS) by regulating drug response pathways. These miRNAs show promise as biomarkers for predicting treatment effectiveness in OS patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma (OS) is a primary bone cancer affecting young individuals, often treated with cisplatin (CDDP).
- Cisplatin resistance is a significant clinical challenge, limiting treatment efficacy and leading to severe side effects.
- Understanding the molecular mechanisms of CDDP resistance is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To review and discuss microRNAs (miRNAs) associated with cisplatin (CDDP) response in osteosarcoma (OS) cells.
- To elucidate the role of miRNAs in regulating CDDP resistance and sensitivity.
- To highlight miRNAs as potential biomarkers for predicting CDDP response in OS.
Main Methods:
- Literature review of studies investigating miRNAs and CDDP response in osteosarcoma.
- Analysis of miRNA-mediated regulation of cellular processes involved in multidrug resistance (MDR).
- Synthesis of findings on how miRNAs impact drug efflux, detoxification, signaling pathways, apoptosis, and autophagy.
Main Results:
- The majority of identified miRNAs enhance CDDP sensitivity in OS cells.
- These miRNAs modulate key pathways including signaling, apoptosis, drug transport, and autophagy.
- miRNAs are implicated in overcoming multidrug resistance (MDR) mechanisms in osteosarcoma.
Conclusions:
- MicroRNAs play a significant role in regulating cisplatin sensitivity and resistance in osteosarcoma.
- miRNAs offer a promising avenue for novel therapeutic interventions against CDDP-resistant OS.
- miRNAs can serve as reliable non-invasive biomarkers for predicting CDDP treatment response in osteosarcoma patients.
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