Xu Jing-Li, Yuan Li, Tang Yan-Cheng, Xu Zhi-Yuan, Xu Han-Dong, Cheng Xiang-Dong, Qin Jiang-Jiang
Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Hangzhou, China.
Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China.
Front Cell Dev Biol. 2020 Dec 3;8:621428. doi: 10.3389/fcell.2020.621428. eCollection 2020.
Gastric cancer is the third most common cause of cancer-related death worldwide. Drug resistance is the main inevitable and vital factor leading to a low 5-year survival rate for patients with gastric cancer. Autophagy, as a highly conserved homeostatic pathway, is mainly regulated by different proteins and non-coding RNAs (ncRNAs) and plays dual roles in drug resistance of gastric cancer. Thus, targeting key regulatory nodes in the process of autophagy by small molecule inhibitors or activators has become one of the most promising strategies for the treatment of gastric cancer in recent years. In this review, we provide a systematic summary focusing on the relationship between autophagy and chemotherapy resistance in gastric cancer. We comprehensively discuss the roles and molecular mechanisms of multiple proteins and the emerging ncRNAs including miRNAs and lncRNAs in the regulation of autophagy pathways and gastric cancer chemoresistance. We also summarize the regulatory effects of autophagy inhibitor and activators on gastric cancer chemoresistance. Understanding the vital roles of autophagy in gastric cancer chemoresistance will provide novel opportunities to develop promising therapeutic strategies for gastric cancer.
胃癌是全球癌症相关死亡的第三大常见原因。耐药性是导致胃癌患者5年生存率较低的主要不可避免且至关重要的因素。自噬作为一种高度保守的稳态途径,主要受不同蛋白质和非编码RNA(ncRNAs)调控,在胃癌耐药中发挥双重作用。因此,近年来通过小分子抑制剂或激活剂靶向自噬过程中的关键调控节点已成为治疗胃癌最有前景的策略之一。在本综述中,我们系统总结了聚焦于胃癌中自噬与化疗耐药之间的关系。我们全面讨论了多种蛋白质以及包括微小RNA(miRNAs)和长链非编码RNA(lncRNAs)在内的新兴ncRNAs在自噬途径调控及胃癌化疗耐药中的作用和分子机制。我们还总结了自噬抑制剂和激活剂对胃癌化疗耐药的调控作用。了解自噬在胃癌化疗耐药中的重要作用将为开发有前景的胃癌治疗策略提供新机会。