Phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), an essential enzyme involved in de novo purine biosynthesis, is connected with formation of various tumors. However, the specific biological roles and related mechanisms of PAICS in gastric cancer (GC) remain unclear. In the present study, we identified for the first time that PAICS was significantly upregulated in GC and high expression of PAICS was correlated with poor prognosis of patients with GC. In addition, knockdown of PAICS significantly induced cell apoptosis, and inhibited GC cell growth both in vitro and in vivo. Mechanistic studies first found that PAICS was engaged in DNA damage response, and knockdown of PAICS in GC cell lines induced DNA damage and impaired DNA damage repair efficiency. Further explorations revealed that PAICS interacted with histone deacetylase HDAC1 and HDAC2, and PAICS deficiency decreased the expression of DAD51 and inhibited its recruitment to DNA damage sites by impairing HDAC1/2 deacetylase activity, eventually preventing DNA damage repair. Consistently, PAICS deficiency enhanced the sensitivity of GC cells to DNA damage agent, cisplatin (CDDP), both in vitro and in vivo. Altogether, our findings demonstrate that PAICS plays an oncogenic role in GC, which act as a novel diagnosis and prognostic biomarker for patients with GC.

磷酸核糖基氨基咪唑羧化酶，磷酸核糖基氨基咪唑琥珀酰羧酰胺合成酶（PAICS）是参与从头嘌呤生物合成的必需酶，与各种肿瘤的形成有关。但是，尚不清楚PAICS在胃癌（GC）中的具体生物学作用和相关机制。在本研究中，我们首次发现PAICS在GC中显着上调，而PAICS的高表达与GC患者的预后不良相关。另外，敲低PAICS显着诱导细胞凋亡，并在体外和体内均抑制GC细胞生长。机理研究首先发现，PAICS参与了DNA损伤反应，而GC细胞系中PAICS的敲低诱导了DNA损伤并损害了DNA损伤修复效率。进一步的研究表明，PAICS与组蛋白脱乙酰基酶HDAC1和HDAC2相互作用，并且PAICS缺乏通过降低HDAC1 / 2脱乙酰基酶活性来降低DAD51的表达并抑制其募集至DNA损伤位点，最终阻止DNA损伤修复。一致地，无论是在体内还是体外，PAICS缺乏症都会增强GC细胞对DNA损伤剂顺铂（CDDP）的敏感性。总而言之，我们的研究结果表明，PACS在GC中起着致癌作用，它是GC患者的新型诊断和预后生物标志物。PAICS缺乏症在体外和体内均增强了GC细胞对DNA损伤剂顺铂（CDDP）的敏感性。总而言之，我们的研究结果表明，PACS在GC中起着致癌作用，它是GC患者的新型诊断和预后生物标志物。PAICS缺乏症在体外和体内均增强了GC细胞对DNA损伤剂顺铂（CDDP）的敏感性。总而言之，我们的研究结果表明，PACS在GC中起着致癌作用，它是GC患者的新型诊断和预后生物标志物。