title: Down-regulation of ASIC1 suppressed gastric cancer via inhibiting autophagy.
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.
authors.affiliation: Department of Pathology, Bengbu Medical College, Bengbu 233000, China; Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Bengbu Medical College, Bengbu 233000, China; Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
authors.forename: Shiwu
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Oncology Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Bengbu Medical College, Bengbu 233000, China; Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China. Electronic address: chai_damin1981@sina.com.
authors.forename: Damin
authors.initials: D
authors.lastname: Chai
authors.affiliation: Department of Pathology, Bengbu Medical College, Bengbu 233000, China; Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China. Electronic address: ganhuaiyong_21@sohu.com.
authors.forename: Huaiyong
authors.initials: H
authors.lastname: Gan
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics*; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: C568266:ASIC1 protein, human; D062565:Acid Sensing Ion Channels; D034741:RNA, Small Interfering
keywords: ASIC1; ATG5; Autophagy; Gastric cancer; Knockdown