microRNA调控自噬在骨肉瘤化疗耐药中作用的研究进展

Research advances in the microRNAs regulation of autophagy in chemoresistance of osteosarcoma

骨肉瘤(osteosarcoma,OS)是青少年最常见的原发性恶性骨肿瘤,它好发于长骨的干骺端,而股骨远端和胫骨近端的发病率占其50%。其每年发病率为3/100万,其中男女比例为1∶1.4 )[1-2])。OS易通过血液转移到其它器官,尤其肺部。少数情况下可转移到大脑、前列腺和其它组织[3-4]。

Osteosarcoma (OS)is a primary malignant bone tumor that occurs in adolescents with a high metastatic rate and mortality. With the rapid development of surgery and neoadjuvant chemotherapy, the 5-year survival rate with no metastasis has been significantly improved. Comprehensive treatment such like neoadjuvant chemotherapy combined with limb salvage surgery has become the main treatment method for OS. However, the development of chemotherapy resistance can lead to the recurrence and metastasis of OS, which poses a challenge to the clinical efficacy of chemotherapy. Studies have reported that chemotherapy resistance of OS was a complex process involving multi-level, multi-factor, multi-gene and multi-signal pathways. The study of autophagy, microRNA and OS chemoresistance mechanism is a hot topic in recent research, but its regulation mechanism is still unclear. Therefore, this review will detail the interaction mechanisms between autophagy, microRNA, microRNA regulating autophagy-related factors and OS chemoresistance, and graphically illustrate autophagy, microRNA changes and OS chemosensitivity and drug resistance. Effects of up-regulation and down-regulation of microRNA on the resistance to OS chemotherapy in autophagy signaling are discussed. Furthermore, it is important to review the role of microRNAs in the regulation of mammalian rapamycin target protein (mTOR), high mobility group protein (HMGB), Beclin-1 and other autophagy-related genes in OS chemoresistance to further reveal OS chemoresistance, potential molecular mechanisms of production and development.