Agmatinase（AGMAT）是一种酶，能将精胺酸水解为腐胺和尿素。我们探究了在结直肠癌（CRC）中AGMAT的作用。通过进行增强和减弱功能的实验，我们研究了AGMAT在CRC细胞增殖、细胞周期进程和细胞凋亡中的作用。我们还通过将小鼠暴露于azoxy甲烷（AOM）和戊二酸二钠（DSS）建立了结肠炎相关性结直肠癌（CAC）模型，并通过介导短发夹RNA（shRNA）的腺相关病毒9（AAV9）靶向沉默AGMAT基因表达。体外实验表明，AGAMT的过量表达加速了CRC细胞的增殖并抑制了细胞凋亡，而AGMAT的靶向沉默则产生了相反的效果。有趣的是，致癌转录因子c-Myc可结合AGMAT启动子，并转录增加CRC细胞中AGMAT的表达。此外，在AOM/DSS处理的小鼠结肠中，c-Myc和AGMAT均上调表达，并靶向沉默AGMAT可显著减轻小鼠的结肠炎，并通过增加结肠长度，减轻隐窝损伤以及降低结肠组织中炎性指标（髓过氧化物酶、白细胞介素-6、肿瘤坏死因子-α、诱导型一氧化氮合酶和p65磷酸化）的水平来进行证实。值得注意的是，AGMAT的靶向沉默既减少了肿瘤数量和大小，也降低了AOM/DSS处理的小鼠结肠中增殖细胞核抗原（PCNA）的表达，并抑制了蛋白激酶B（AKT）和外周信号调节激酶（ERK）的磷酸化。总的来说，我们确定了AGMAT在CRC中促进肿瘤进展的作用。本研究结果对于寻找CRC潜在治疗靶点将有所助益。

Agmatinase (AGMAT) is an enzyme that hydrolyzes agmatine to putrescine and urea. Here, we explored the functions of AGMAT in colorectal cancer (CRC). By performing gain-of-function and loss-of-function experiments, we investigated the roles of AGMAT in proliferation, cell cycle progression, and apoptosis of CRC cells. We also established a colitis-associated colorectal cancer (CAC) model by challenging mice with azoxymethane (AOM) and dextran sodium sulfate (DSS), and we subsequently silenced AGMAT expression in mice by adeno-associated virus 9 (AAV9)-mediated delivery of short hairpin RNA (shRNA). In vitro experiments showed that overexpression of AGAMT accelerated the proliferation and inhibited the apoptosis of CRC cells, and AGMAT knockdown exhibited the opposite effects. Interestingly, the oncogenic transcription factor c-Myc could bind to the AGMAT promoter and transcriptionally increase AGMAT expression in CRC cells. Additionally, c-Myc and AGMAT were upregulated in the colon of AOM/DSS-treated mice, and AGMAT silencing significantly mitigated colitis in AOM/DSS-treated mice, as evidenced by the increased colon length, attenuated crypt damage, and reduced levels of inflammatory indicators (myeloperoxidase, interleukin-6, tumor necrosis factor-α, inducible nitric oxide synthase, and phosphorylated p65) in colon tissues. Notably, AGMAT silencing decreased both the number and size of tumors, reduced expression of proliferating cell nuclear antigen (PCNA), and inhibited the phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) in the colon of AOM/DSS-treated mice. Overall, we determined that AGMAT facilitates tumor progression in CRC. Our findings will be helpful in the search for potential therapeutic targets for CRC.