Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 53, Issue 6, Pages 2769-2779Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2018.4593
Keywords
miR-874; multiple-drug resistance; gastric cancer; autophagy-related 16-like 1
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Funding
- Huai'an International Science and Technology Cooperation Research Project [HAC201709]
- 333 High-Level Talents Training Project of Jiangsu Province [BRA2017247]
- Jiangsu Province Young Medical Talent Project [QNRC 2016423]
- QNRC [2016423]
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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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