Down-regulation of ASIC1 suppressed gastric cancer via inhibiting autophagy

• Published in: Gene Vol. 608; pp. 79 - 85
• Main Authors: Zhang, Qiong, Wu, Shiwu, Zhu, Jinhai, Chai, Damin, Gan, Huaiyong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.04.2017
• Subjects: Acid Sensing Ion Channels - genetics; Animals; ASIC1; ATG5; Autophagy; Autophagy - drug effects; Autophagy - genetics; Cells, Cultured; Down-Regulation - drug effects; Down-Regulation - genetics; Female; Gastric cancer; Gene Expression Regulation, Neoplastic - drug effects; Gene Knockdown Techniques; Humans; Knockdown; Mice; Mice, Inbred BALB C; Mice, Nude; RNA, Small Interfering - pharmacology; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Xenograft Model Antitumor Assays; Knockdown; ASICs; Gastric cancer; Autophagy; ATG5; ASIC1
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2017.01.014

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. •ASIC1 and ATG5 are enriched in gastric cancer tissue in patients.•ASIC1 regulates ATG5 gene expression in SGC-7901 cells.•ASIC1 knockdown extends the survival rate of animals.•ASIC1 knockdown inhibits the tumor growth in the xenograft model.