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Down-regulation of ASIC1 suppressed gastric cancer via inhibiting autophagy
Qiong Zhang1, Shiwu Wu1, Jinhai Zhu2
1Department of Pathology, Bengbu Medical College, Bengbu 233000, China; Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
Abstract:
As autophagy has anti-apoptosis effect and accelerates cell survival, many studies start to target autophagy as a therapeutic strategy for cancer. Acid-sensing ion channels (ASICs) was reported to activate autophagy. However, whether ASICs can regulate gastric cancer through autophagy is unknown. The differentially expressed genes in normal gastric tissue and gastric cancer tissue in patients were investigated by RNA-seq. Expression of ASIC1 and autophagy related 5 (ATG5) was further confirmed by real-time PCR. Effects of knockdown expression of ASIC1 and ATG5 on the growth of gastric SGC-7901 cells were assayed by CCK-8 kit. The animal survival rate and tumor volume in murine heterotopic xenograft model was assayed. The expression of autophagy related genes was enriched in gastric cancer tissue in patients, including ASIC1 and ATG5. Knockdown expression of ASIC1 and ATG5 inhibits the growth of SGC-7901 cells, respectively. ASIC1 regulates ATG5 gene expression in SGC-7901 cells. ASIC1 knockdown extended the survival rate of animals and inhibited the tumor volume in the murine heterotopic xenograft model. This study showed that downregulation of ASIC1 inhibits gastric cancer growth via decreasing autophagy, therefore strongly suggests a therapeutic role for ASIC1 in gastric cancer.
Insights
Targeting acid-sensing ion channels (ASICs) may treat gastric cancer. Downregulating ASIC1 inhibits cancer growth by reducing autophagy, offering a potential therapeutic strategy for gastric cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Autophagy plays a role in cancer cell survival and is a therapeutic target.
- Acid-sensing ion channels (ASICs) are known to activate autophagy.
- The role of ASICs in gastric cancer progression via autophagy remains unclear.
Purpose of the Study:
- To investigate the role of ASICs, specifically ASIC1, in gastric cancer.
- To determine if ASICs regulate gastric cancer through autophagy.
- To explore ASIC1 as a potential therapeutic target for gastric cancer.
Main Methods:
- RNA sequencing to identify differentially expressed genes in gastric cancer.
- Real-time PCR to confirm expression of ASIC1 and autophagy-related gene 5 (ATG5).
- Cell proliferation assays (CCK-8) and xenograft models in mice to assess tumor growth and survival rates.
Main Results:
- Autophagy-related genes, including ASIC1 and ATG5, are upregulated in gastric cancer tissues.
- Knockdown of ASIC1 or ATG5 inhibits gastric cancer cell growth (SGC-7901).
- ASIC1 knockdown reduces tumor volume and improves survival rates in a murine model, mediated by decreased autophagy.
Conclusions:
- ASIC1 expression is elevated in gastric cancer and promotes tumor growth.
- ASIC1 regulates autophagy in gastric cancer cells.
- Downregulation of ASIC1 inhibits gastric cancer progression by suppressing autophagy, suggesting ASIC1 as a potential therapeutic target.
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