Chen Hong, Wang Wei, Xiao Caizhi, Xia Dongqin, Li Fangfei, Liu Shaoyong
Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, China.
Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, China.
Ann Transl Med. 2021 Sep;9(17):1378. doi: 10.21037/atm-21-3127.
Non-small cell lung cancer (NSCLC) has a poor prognosis and is the most common cause of cancer-related deaths worldwide. Aminoacylase 1 (ACY1) plays a promoting role in some cancers, but its role in NSCLC is still unclear.
Immunohistochemistry, Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting assays were used to determine ACY1 expression patterns in NSCLC tissues and cell lines. The clinical significance of ACY1 in NSCLC was evaluated by χ test and Kaplan-Meier analysis. MTT, flow cytometry, wound healing, and Transwell assays were performed to assess cell growth, apoptosis, migration, invasion, and tumorigenesis under different treatments. Male athymic BALB/C nude mice were used for xenotransplantation experiments.
The results showed that ACY1 expression was elevated in NSCLC tissue samples and cells, and high ACY1 expression predicted an advanced clinical process and shorter overall survival in patients with NSCLC. Overexpression of ACY1 significantly increased cell growth, migration, invasion, and tumorigenesis, and reduced cell apoptosis, indicating that ACY1 functions as an oncogene in NSCLC. Moreover, ACY1 decreased phosphatase and tensin homolog (PTEN) expression, increased its ubiquitination, and activated PI3K/AKT signaling. Overexpression of PTEN diminished the effects of ACY1 upregulation on cell tumorigenesis promotion.
This study reveals that ACY1 may promote the progression of NSCLC via activating PI3K/AKT signaling in a PTEN-dependent manner. Our study may provide a better understanding of the pathogenesis and development of NSCLC.
非小细胞肺癌（NSCLC）预后较差，是全球癌症相关死亡的最常见原因。氨基酰化酶1（ACY1）在某些癌症中起促进作用，但其在NSCLC中的作用仍不清楚。
采用免疫组织化学、逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹分析来确定NSCLC组织和细胞系中ACY1的表达模式。通过χ检验和Kaplan-Meier分析评估ACY1在NSCLC中的临床意义。进行MTT、流式细胞术、伤口愈合和Transwell分析，以评估不同处理下的细胞生长、凋亡、迁移、侵袭和肿瘤发生情况。雄性无胸腺BALB/C裸鼠用于异种移植实验。
结果显示，ACY1在NSCLC组织样本和细胞中表达升高，ACY1高表达预示着NSCLC患者临床进程晚期和总生存期较短。ACY1过表达显著增加细胞生长、迁移、侵袭和肿瘤发生，并减少细胞凋亡，表明ACY1在NSCLC中作为癌基因发挥作用。此外，ACY1降低磷酸酶和张力蛋白同源物（PTEN）的表达，增加其泛素化，并激活PI3K/AKT信号通路。PTEN过表达减弱了ACY1上调对细胞肿瘤发生促进作用的影响。
本研究揭示ACY1可能通过以PTEN依赖的方式激活PI3K/AKT信号通路促进NSCLC的进展。我们的研究可能有助于更好地理解NSCLC的发病机制和发展。
