miR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1
Haijin Huang1, Jie Tang2, Lei Zhang2
1Department of General Surgery, Hongze District People's Hospital, Huai'an, Jiangsu 223100, P.R. China.
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.
Insights
MicroRNA-874 can overcome multidrug resistance in gastric cancer by inhibiting autophagy through the ATG16L1 gene. This finding offers a potential strategy to improve chemotherapy effectiveness for gastric cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chemotherapy is a key treatment for gastric cancer (GC), but its efficacy is often limited by multidrug resistance (MDR).
- MicroRNA (miR)-874 has previously been implicated in tumor growth, apoptosis, and angiogenesis.
- The specific role and mechanisms of miR-874 in GC drug resistance remain to be fully elucidated.
Purpose of the Study:
- To investigate the role and underlying mechanisms of miR-874 in multidrug resistance (MDR) in gastric cancer (GC).
- To determine if miR-874 can sensitize GC cells to chemotherapy.
- To identify the molecular targets and pathways regulated by miR-874 in the context of drug resistance.
Main Methods:
- In vitro experiments involving overexpression of miR-874 in GC cells.
- Reporter gene assays to identify direct targets of miR-874.
- Western blot analysis to confirm protein expression levels.
- Assessment of autophagy-related protein 16-like 1 (ATG16L1) expression and its association with autophagy.
- Evaluation of the effect of ATG16L1 knockdown and autophagy inhibition on GC cell sensitivity to chemotherapy.
Main Results:
- Overexpression of miR-874 reversed drug resistance in gastric cancer cells in vitro.
- Autophagy-related 16-like 1 (ATG16L1) was identified as a direct target of miR-874.
- ATG16L1 expression was positively correlated with autophagy.
- Reducing ATG16L1 expression and inhibiting autophagy sensitized GC cells to chemotherapy.
- A regulatory loop involving miR-874, ATG16L1, and autophagy was identified as crucial in GC multidrug resistance.
Conclusions:
- MiR-874 inhibits autophagy and sensitizes gastric cancer cells to chemotherapy by targeting ATG16L1.
- The miR-874/ATG16L1/autophagy pathway plays a significant role in mediating multidrug resistance in GC.
- MiR-874 demonstrates potential as a prognostic factor and a therapeutic target for overcoming chemotherapeutic resistance in GC.
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