Department of General Surgery, Hongze District People's Hospital, Huai'an, Jiangsu 223100, P.R. China.
Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
Int J Oncol. 2018 Dec;53(6):2769-2779. doi: 10.3892/ijo.2018.4593. Epub 2018 Oct 11.
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.
化疗是胃癌（GC）的重要治疗选择；然而，由于耐药性，尤其是多药耐药（MDR），化疗通常会失败。在我们之前的研究中，已经证明 microRNA（miR）-874 在肿瘤生长、细胞凋亡和血管生成中发挥着重要作用。在本研究中，研究了 miR-874 在 GC 中的 MDR 中的精确作用和潜在机制。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 Western blot 分析，自噬相关 16 样 1（ATG16L1）被鉴定为 miR-874 的直接靶标。ATG16L1 也被证明与自噬呈正相关。降低 ATG16L1 的表达并抑制自噬的发生使 GC 细胞对化疗敏感。因此，miR-874/ATG16L1/自噬调节环在 GC 中的 MDR 中发挥着重要作用。此外，miR-874 可能作为 GC 的预后因素。总的来说，miR-874 可以通过靶基因 ATG16L1 抑制自噬并使 GC 细胞对化疗敏感，这突出了 miR-874 在化疗耐药性中的潜在临床应用。
