miR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1

Huang,Haijin; Tang,Jie; Zhang,Lei; Bu,Yanzhi; Zhang,Xiaoyu

doi:10.3892/ijo.2018.4593

miR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1

Authors:
- Haijin Huang
- Jie Tang
- Lei Zhang
- Yanzhi Bu
- Xiaoyu Zhang
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Affiliations: 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, Department of General Surgery, Lianshui Country People's Hospital, Lianshui Country, Huai'an, Jiangsu 223400, P.R. China, Department of General Surgery, Huai'an Second People's Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu 223001, P.R. China
Published online on: October 11, 2018 https://doi.org/10.3892/ijo.2018.4593
Pages: 2769-2779

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Abstract

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.

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