Department 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.
Pathol Res Pract. 2023 Sep;249:154743. doi: 10.1016/j.prp.2023.154743. Epub 2023 Aug 6.
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.
骨肉瘤（OS）是一种源自间充质细胞的侵袭性骨肿瘤。它被认为是第八大常见的儿童癌症，主要影响青少年和年轻人的胫骨和股骨。OS 通常可以通过 MRI 和手术活检相结合来诊断。动脉内顺铂（CDDP）和阿霉素是 OS 治疗的方法之一。CDDP 通过干扰 DNA 复制来诱导肿瘤细胞死亡。尽管 CDDP 在改善 OS 患者的临床并发症方面发挥着关键作用，但这些患者中存在着很高的 CDDP 耐药比例。CDDP 的长期给药在正常组织和器官中也有严重的副作用。因此，应该阐明 CDDP 耐药的分子机制，以确定 OS 的新治疗方法。多药耐药（MDR）可能是由各种细胞和分子过程引起的，如药物外排、解毒和信号通路。微小 RNA（miRNA）是通过参与 MDR 的靶基因的转录后调控来调节 CDDP 反应的关键调节剂。在本综述中，我们讨论了与 OS 细胞中 CDDP 反应相关的所有 miRNA。结果表明，大多数报道的 miRNA 通过调节信号通路、细胞凋亡、转运体和自噬来增加 OS 细胞对 CDDP 的敏感性。本综述强调了 miRNA 作为 OS 患者预测 CDDP 反应的可靠非侵入性标志物。
