miR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1
miR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1
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DOI：
10.3892/ijo.2018.4593
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发表时间：
2018-12-01
影响因子：
5.2
通讯作者：
Zhang, Xiaoyu
中科院分区：
文献类型：
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作者：
Huang, Haijin;Tang, Jie;Zhang, Xiaoyu
化疗是胃癌的重要治疗手段，但化疗往往因耐药，特别是多药耐药（MDR）而失败。在我们以前的研究中，microRNA（miR）-874被证明在肿瘤生长、凋亡和血管生成中起重要作用。本研究旨在探讨miR-874在胃癌多药耐药中的作用及其机制。miR-874的过表达在体外逆转了癌细胞的耐药性。根据报告基因和蛋白质印迹分析，自噬相关16样1（ATG 16 L1）被鉴定为miR-874的直接靶点。ATG 16 L1也被证明与自噬正相关。降低ATG 16 L1的表达和抑制自噬的发生使胃癌细胞对化疗敏感。因此，miR-874/ATG 16 L1/自噬调控环被证明在GC的MDR中起重要作用。此外，miR-874可用作GC的预后因子。总体而言，miR-874可以通过靶基因ATG 16 L1抑制自噬并使GC细胞对化疗敏感，突出了miR-874在化疗耐药性中的潜在临床应用。
Chemotherapy is an important treatment option for gastric cancer (GC); however, chemotherapy usually fails due to drug resistance, particularly multidrug resistance (MDR). In our previous studies, microRNA (miR)-874 was demonstrated to serve an important role in tumour growth, apoptosis and angiogenesis. In the present study, the precise roles and underlying mechanisms of miR-874 in MDR were investigated in GC. The overexpression of miR-874 reversed cancer cell drug resistance in vitro. According to reporter gene and western blot assays, Autophagy-related 16-like 1 (ATG16 L1) was identified as a direct target of miR-874. ATG16L1 was also demonstrated to be positively associated with autophagy. Reducing the expression of ATG16L1 and inhibiting the occurrence of autophagy sensitized GC cells to chemotherapy. Thus, the miR-874/ATG16L1/autophagy regulatory loop was demonstrated to serve an important role in MDR in GC. Furthermore, miR-874 may be used as a prognostic factor in GC. Overall, miR-874 could inhibit autophagy and sensitize GC cells to chemotherapy via the target gene ATG16L1, highlighting the potential clinical application of miR-874 in chemotherapeutic resistance.