Aminoacylase 1 (ACY-1) Mediates the Proliferation and Migration of Neuroblastoma Cells in Humans Through the ERK/Transforming Growth Factor β (TGF-β) Signaling Pathways

Chen, Zimin; Gao, Jiahui; Sun, Jun; Wu, Zhouguang; Wang, Bin

doi:10.12659/msm.928813

Cited by 4 publications

(3 citation statements)

References 33 publications

(20 reference statements)

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“…ACY1 was recently shown to play complex roles in carcinogenesis. First, ACY1 was found to suppress the proliferation and induce the apoptosis of neuroblastoma cells by inhibiting the ERK/TGF-β pathway 27 . By contrast, ACY1 was reported to promote the progression of non-small-cell lung cancer by activating the PTEN-PI3K-AKT signaling pathway 28 .…”

Section: Discussionmentioning

confidence: 99%

ACY1-mediated deacetylation of GSTP1 at lysine 30 suppresses cisplatin resistance in epithelial ovarian cancer

Zheng¹,

Zheng²,

Hou

et al. 2022

Preprint

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Resistance to platinum-based chemotherapy is the major limitation to the improvement of epithelial ovarian cancer (EOC) prognosis. Aminoacylase-1 (ACY1) hydrolyzes acylated l-amino acids and N-acetylated proteins; however, the roles of ACY1 in EOC and platinum resistance remain unknown. Accordingly, this study explored the biological functions and clinical significance of ACY1 in the resistance of EOC to cisplatin therapy. We found that lower levels of ACY1 were associated with worse prognosis and platinum-based chemoresistance in EOC. Moreover, ACY1 significantly sensitized EOC cells to cisplatin in vitro and in vivo. Mechanistically, ACY1 deacetylated glutathione S-transferase P1 (GSTP1) at lysine 30, which triggered its degradation and thereby reduced GSTP1 stability. Thus, ACY1 attenuated the intracellular reactive oxygen species (ROS) elimination and DNA damage repair. Finally, histone deacetylase 4 (HDAC4) downregulated ACY1 transcription by suppressing histone H3 lysine 27 acetylation on the ACY1 promoter, and inhibiting HDAC4 reversed cisplatin resistance in EOC cells. Collectively, these results revealed an HDAC4–ACY1–GSTP1 axis as vital signaling for cisplatin resistance in EOC. This suggested that ACY1 might be a novel mediator in EOC chemoresistance and HDAC4 inhibitors could be used to overcome platinum resistance in patients with low expression of ACY1.

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Section: Discussionmentioning

confidence: 99%

ACY1-mediated deacetylation of GSTP1 at lysine 30 suppresses cisplatin resistance in epithelial ovarian cancer

Zheng¹,

Zheng²,

Hou

et al. 2022

Preprint

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show abstract

“…Several studies have shown the roles of ACY1 in diverse cancers. For instance, Chen et al demonstrated that ACY1 regulated the proliferation, migration, and invasion of human neuroblastoma cells via the extracellular signal-regulated protein kinase 1/2 and transforming growth factor-β1 signaling pathways [ 44 ], and Xu et al [ 45 ] revealed that targeting the ACY1 gene might regulate HER2 and TRAIL expression levels and reduce the occurrence and inhibit the development of rectal cancer. In addition, ACY1 promoted the progression of non-small cell lung cancer by activating phosphoinositide 3-kinase/Akt signaling in a phosphatase and tensin homolog-dependent manner [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

ACY1 Downregulation Enhances the Radiosensitivity of Cetuximab-Resistant Colorectal Cancer by Inactivating the Wnt/β-Catenin Signaling Pathway

Shan

Dai

Zhang

et al. 2022

Cancers

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Treatment of cetuximab-resistant colorectal cancer (CRC) is a global healthcare problem. This study aimed to assess the effects of radiotherapy on cetuximab-resistant CRC and explore the underlying mechanism. We established a cetuximab-resistant HCT116 cell line (HCT116-R) by extracorporeal shock. Differentially expressed mRNAs were screened from cells treated with different radiation doses using second-generation high-throughput sequencing. Sequence data showed that ACY1 was significantly downregulated in HCT116-R cells after irradiation. Analysis of the GEO and TCGA datasets revealed that high ACY1 expression was associated with lymph node metastasis and a poor prognosis in CRC patients. In addition, immunohistochemistry results from CRC patients revealed that ACY1 protein expression was related to cetuximab resistance and lymph node metastasis. These findings suggested that ACY1 may function as an oncogene to promote CRC progression and regulate the radiosensitivity of cetuximab-resistant CRC. As expected, ACY1 silencing weakened the proliferation, migration, and invasion abilities of HCT116-R cells after radiotherapy. Mechanistically, TCGA data demonstrated that ACY1 expression was closely related to the Wnt/β-catenin pathway in CRC. We validated that radiotherapy first reduced β-catenin levels, followed by decreased expression of the metastasis-related protein E-cadherin. Silencing ACY1 dramatically enhanced these changes in β-catenin and E-cadherin after radiotherapy. In conclusion, ACY1 downregulation could enhance the radiosensitivity of cetuximab-resistant CRC by inactivating Wnt/β-catenin signaling, implying that ACY1 may serve as a radiotherapy target for cetuximab-resistant CRC.

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“…However, ACY1 was reported to be overexpressed in colorectal cancer (CRC), and knockdown of ACY1 significantly inhibited proliferation and induced cell apoptosis (10,11). It is showed that in neuroblastoma, ACY1 has the effect of inhibiting proliferation and metastasis (12). Nevertheless, the roles of ACY1 in NSCLC remain unclear.…”

Section: Introductionmentioning

confidence: 99%

ACY1 regulating PTEN/PI3K/AKT signaling in the promotion of non-small cell lung cancer progression

Chen¹,

Wang²,

Xiao³

et al. 2021

Ann Transl Med

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Background: 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. Methods: 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 2 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.Results: 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.Conclusions: 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.

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Aminoacylase 1 (ACY-1) Mediates the Proliferation and Migration of Neuroblastoma Cells in Humans Through the ERK/Transforming Growth Factor β (TGF-β) Signaling Pathways

Cited by 4 publications

References 33 publications

ACY1-mediated deacetylation of GSTP1 at lysine 30 suppresses cisplatin resistance in epithelial ovarian cancer

ACY1-mediated deacetylation of GSTP1 at lysine 30 suppresses cisplatin resistance in epithelial ovarian cancer

ACY1 Downregulation Enhances the Radiosensitivity of Cetuximab-Resistant Colorectal Cancer by Inactivating the Wnt/β-Catenin Signaling Pathway

ACY1 regulating PTEN/PI3K/AKT signaling in the promotion of non-small cell lung cancer progression

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