Zhang Qiong, Wu Shiwu, Zhu Jinhai, Chai Damin, Gan Huaiyong
Department of Pathology, Bengbu Medical College, Bengbu 233000, China; Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
Department of Oncology Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
Gene. 2017 Apr 15;608:79-85. doi: 10.1016/j.gene.2017.01.014. Epub 2017 Jan 19.
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.
由于自噬具有抗凋亡作用并能加速细胞存活，许多研究开始将自噬作为癌症的一种治疗策略。据报道，酸敏感离子通道（ASICs）可激活自噬。然而，ASICs是否能通过自噬调节胃癌尚不清楚。通过RNA测序研究了患者正常胃组织和胃癌组织中的差异表达基因。通过实时PCR进一步证实了ASIC1和自噬相关蛋白5（ATG5）的表达。用CCK-8试剂盒检测ASIC1和ATG5基因敲低表达对胃SGC-7901细胞生长的影响。检测小鼠异位移植模型中的动物存活率和肿瘤体积。自噬相关基因的表达在患者的胃癌组织中富集，包括ASIC1和ATG5。ASIC1和ATG5基因敲低表达分别抑制SGC-7901细胞的生长。ASIC1调节SGC-7901细胞中ATG5基因的表达。在小鼠异位移植模型中，ASIC1基因敲低延长了动物的存活率并抑制了肿瘤体积。本研究表明，ASIC1的下调通过降低自噬来抑制胃癌生长，因此强烈提示ASIC1在胃癌中具有治疗作用。
