Cardiovascular Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
IUBMB Life. 2020 Jul;72(7):1306-1321. doi: 10.1002/iub.2277. Epub 2020 Mar 31.
Osteosarcoma (OS) is a kind of primary bone cancer that is considered as the leading cause of children death. Surgery and chemotherapy are considered as common treatment approaches for OS; the rate of survival for patients is almost 60-70%. Besides the used therapeutic approaches, it seems that there is a crucial need to launch new treatments for OS. In this regard, more understanding about cellular and molecular pathways involved in OS can contribute to recovery and develop new therapeutic platforms. Autophagy is a cellular machinery that digests and degrades dysfunctional proteins and organelles, so it can regulate the cell proliferation and survival. Most of the time, OS cells use autophagy to increase their survival and proliferation and to gain the ability to resist chemotherapy. Although, there are several controversial evidences on how OS cells use autophagy. A variety of cellular and molecular pathways, that is, microRNAs (miRNAs) can modulate autophagy. MiRNAs are some endogenous, approximately 22 nucleotide RNAs that have an important role in posttranscriptional regulation of mRNAs by targeting them. There are many evidences that the various miRNA expressions in OS cells are dysregulated, so it can propel a normal cell to cancerous one by influencing the cell survival, apoptosis, and autophagy, and eventually increased chemoresitance. Hence, miRNAs can be considered as new biomarkers for OS diagnosis, and according to the role of autophagy in OS progression, miRNAs can use inhibiting or promoting autophagy agents. The present review summarizes the effects of aberrant expression of miRNAs in OS diagnosis and treatment with focus on their roles in autophagy.
骨肉瘤(OS)是一种原发性骨癌,被认为是儿童死亡的主要原因。手术和化疗被认为是 OS 的常见治疗方法;患者的生存率接近 60-70%。除了使用的治疗方法外,似乎迫切需要为 OS 推出新的治疗方法。在这方面,更多地了解参与 OS 的细胞和分子途径可以有助于恢复和开发新的治疗平台。自噬是一种细胞机制,可消化和降解功能失调的蛋白质和细胞器,因此它可以调节细胞增殖和存活。大多数时候,OS 细胞利用自噬来增加其存活和增殖能力,并获得抵抗化疗的能力。尽管 OS 细胞如何利用自噬存在一些有争议的证据。多种细胞和分子途径,即 microRNAs(miRNAs)可以调节自噬。miRNAs 是一些内源性的、大约 22 个核苷酸的 RNA,通过靶向它们在 mRNA 的转录后调节中起重要作用。有大量证据表明,OS 细胞中的各种 miRNA 表达失调,因此通过影响细胞存活、细胞凋亡和自噬,最终增加化疗耐药性,它可以促使正常细胞癌变。因此,miRNAs 可以被视为 OS 诊断的新生物标志物,并且根据自噬在 OS 进展中的作用,miRNAs 可以使用抑制或促进自噬剂。本综述总结了异常表达的 miRNAs 在 OS 诊断和治疗中的作用,重点介绍了它们在自噬中的作用。