Wakefield Biomedical Research Unit, University of Otago, Wellington 6021, New Zealand.
Hum Pathol. 2013 Jun;44(6):1089-97. doi: 10.1016/j.humpath.2012.09.015. Epub 2013 Jan 11.
Aminoacylase 1 (ACY1) is a cytosolic enzyme responsible for amino acid deacylation during intracellular protein degradation. ACY1 has been implicated in a number of human tumor types. However, the exact role of ACY1 in tumor development remains elusive because it was found to be lost in small cell lung cancer and renal cell carcinoma but overexpressed in colorectal cancer (CRC). The present study aims to further clarify the relationship of ACY1 with CRC progression. Immunohistochemical staining was performed in tissue microarrays composed of 120 cases of CRC using a monoclonal anti-ACY1 antibody. Immunoreactivity was analyzed in association with patients' clinicopathologic parameters and survival time. The role of ACY1 in cell proliferation and apoptosis was assessed by silencing its expression in HCT116 cells using a small interfering RNA. Strong expression of ACY1 was found to be significantly associated with more advanced TNM stage, lymph node metastasis, positive vascular invasion, and shorter cancer-specific survival. ACY1 knockdown significantly inhibited cell proliferation and induced apoptosis. We concluded that ACY1 expression in CRC varies with stage and appears to play a role in cell proliferation and apoptosis. Further evaluation of ACY1 as a clinically useful prognostic marker and a potential drug target for CRC would seem worthwhile.
氨基己糖苷酶 1(ACY1)是一种细胞溶质酶,负责细胞内蛋白质降解过程中的氨基酸去酰化。ACY1 与多种人类肿瘤类型有关。然而,ACY1 在肿瘤发展中的确切作用仍然难以捉摸,因为它在小细胞肺癌和肾细胞癌中丢失,但在结直肠癌(CRC)中过度表达。本研究旨在进一步阐明 ACY1 与 CRC 进展的关系。使用单克隆抗 ACY1 抗体在由 120 例 CRC 组成的组织微阵列上进行免疫组织化学染色。根据患者的临床病理参数和生存时间分析免疫反应性。通过使用小干扰 RNA 沉默 HCT116 细胞中的 ACY1 表达来评估 ACY1 在细胞增殖和细胞凋亡中的作用。发现 ACY1 的强表达与更晚期的 TNM 分期、淋巴结转移、阳性血管浸润以及更短的癌症特异性生存时间显著相关。ACY1 敲低显著抑制细胞增殖并诱导细胞凋亡。我们得出结论,CRC 中的 ACY1 表达随阶段而变化,似乎在细胞增殖和细胞凋亡中发挥作用。进一步评估 ACY1 作为一种有临床应用价值的预后标志物和 CRC 的潜在药物靶点似乎是值得的。