ALKBH5 regulates arginase 1 expression in MDSCs and their immunosuppressive activity in tumor-bearing host

Feng, Lili; Li, Min; Ma, Jie; Wang, Wenxin; Wang, Shengjun; Mao, Zhenwei; Zhang, Yue

doi:10.1016/j.ncrna.2024.03.003

Cited by 4 publications

(1 citation statement)

References 36 publications

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“…Arginase is abundantly expressed and active in MDSCs, resulting in enhanced arginine catabolism and a circulating arginine deficit. 219 Arginine, the most versatile amino acid, is vital in controlling T cell proliferation and other processes. 220 Depletion of arginine in the peripheral circulation results in decreased expression of CD3ζ, loss of T‐cell receptor signaling, and inhibition of T‐cell proliferation.…”

Section: Myeloid‐derived Suppressor Cells (Mdscs)mentioning

confidence: 99%

From pancreas to lungs: The role of immune cells in severe acute pancreatitis and acute lung injury

Liu,

Zhu,

Guo

2024

Immunity Inflam & Disease

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BackgroundSevere acute pancreatitis (SAP) is a potentially lethal inflammatory pancreatitis condition that is usually linked to multiple organ failure. When it comes to SAP, the lung is the main organ that is frequently involved. Many SAP patients experience respiratory failure following an acute lung injury (ALI). Clinicians provide insufficient care for compounded ALI since the underlying pathophysiology is unknown. The mortality rate of SAP patients is severely impacted by it.ObjectiveThe study aims to provide insight into immune cells, specifically their roles and modifications during SAP and ALI, through a comprehensive literature review. The emphasis is on immune cells as a therapeutic approach for treating SAP and ALI.FindingsImmune cells play an important role in the complicated pathophysiology ofSAP and ALI by maintaining the right balance of pro‐ and anti‐inflammatory responses. Immunomodulatory drugs now in the market have low thepeutic efficacy because they selectively target one immune cell while ignoring immune cell interactions. Accurate management of dysregulated immune responses is necessary. A critical initial step is precisely characterizing the activity of the immune cells during SAP and ALI.ConclusionGiven the increasing incidence of SAP, immunotherapy is emerging as a potential treatment option for these patients. Interactions among immune cells improve our understanding of the intricacy of concurrent ALI in SAP patients. Acquiring expertise in these domains will stimulate the development of innovative immunomodulation therapies that will improve the outlook for patients with SAP and ALI.

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Section: Myeloid‐derived Suppressor Cells (Mdscs)mentioning

confidence: 99%

From pancreas to lungs: The role of immune cells in severe acute pancreatitis and acute lung injury

Liu,

Zhu,

Guo

2024

Immunity Inflam & Disease

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Unraveling molecular and clinical aspects of ALKBH5 as dual role in colorectal cancer

Memon,

Nadeem,

Sulaiman

et al. 2024

Journal of Pharmacy and Pharmacology

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Objectives This study investigates the dual role of ALKBH5, an eraser enzyme, in colorectal cancer (CRC), focusing on how N6-methyladenosine (m6A) mutations influence CRC development and progression. Methods We reviewed various studies that highlighted the role of ALKBH5 in colorectal cancer (CRC). This includes the impact of ALKBH5 on tumor cell behavior including immune system interactions, invasion, and proliferation in CRC. We also looked into how ALKBH5 acts as a tumor suppressor under different conditions analyzed clinical data to assess the impact of ALKBH5 expression on outcomes in colorectal cancer patients. Key findings In CRC, ALKBH5 plays a dual role. In certain situations, it inhibits the progression of the tumor, but in other circumstances, it promotes tumor growth and immunosuppression. The interaction with RABA5 plays a role in the development of CRC. Having elevated levels of ALKBH5 has been associated with unfavorable patient outcomes, such as reduced survival rates and more advanced cancer stages. Various factors, including tumor differentiation, TNM stages, and carcinoembryonic antigen (CEA) levels, be linked to ALKBH5 expression. Conclusions ALKBH5 plays a complicated and situation-specific role in colorectal cancer (CRC). Targeting ALKBH5 could result in novel therapy options that balance its tumor-promoting and tumor-fighting properties in CRC. Further research into m6A alterations and ALKBH5 could enhance CRC treatment approaches and patient outcomes.

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m ⁶ A demethylase CpALKBH regulates CpZap1 mRNA stability to modulate the development and virulence of chestnut blight fungus

Zhao,

Wei,

Chen

et al. 2024

mBio

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As the most abundant eukaryotic mRNA modification, N 6 -methyladenosine (m 6 A) plays a crucial role in regulating multiple biological processes. This methylation is regulated by methyltransferases and demethylases. However, the regulatory role and mode of action of m 6 A demethylases in fungi remain poorly understood. In this study, we demonstrate that CpALKBH is a demethylase in Cryphonectria parasitica that removes m 6 A modification from single-stranded RNA in vitro . The deletion of CpALKBH resulted in a significant increase in the m 6 A methylation levels, along with decreases in the growth rate, sporulation, and virulence in C. parasitica . Additionally, CpZap1—a transcription factor—was identified as a downstream target of CpALKBH demethylase based on RNA sequencing analysis. We confirmed that CpALKBH demethylase regulates CpZap1 mRNA stability in an m 6 A-dependent manner. Furthermore, through MazF assay, we found that methylation of CpZap1 at position 1935A is regulated by both CpALKBH demethylase and CpMTA1 methyltransferase. CpZap1 significantly influences the fungal phenotype and virulence, thereby restoring the abnormal phenotype observed in ∆ CpALKBH mutants. Collectively, our findings highlight the essential role of CpALKBH as an m 6 A demethylase in the development and virulence of C. parasitica , while also elucidating the molecular mechanisms through which m 6 A modification impacts CpZap1 mRNA stability. IMPORTANCE N 6 -methyladenosine (m 6 A) is the most abundant eukaryotic mRNA modification and is involved in various biological processes. Methyltransferases and demethylases regulate the m 6 A modification, but the regulatory role of m 6 A demethylases in fungi remains poorly understood. Here, we demonstrated that CpALKBH functions as a demethylase in Cryphonectria parasitica . The deletion of CpALKBH leads to a significant increase in m 6 A levels and a reduction in fungal growth, sporulation, and virulence. We identified CpZap1 as a downstream target of CpALKBH, with CpALKBH regulating CpZap1 mRNA stability in an m 6 A-dependent manner. Additionally, our findings indicate that methylation at position 1935A of CpZap1 is regulated by both the CpALKBH demethylase and the CpMTA1 methyltransferase. Given its critical role in fungal development and virulence, overexpression of CpZap1 can rescue abnormal phenotypes of ∆ CpALKBH mutant. Overall, these findings contribute to improving our understanding of the role of m 6 A demethylase in fungi.

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ALKBH5 regulates arginase 1 expression in MDSCs and their immunosuppressive activity in tumor-bearing host

Cited by 4 publications

References 36 publications

From pancreas to lungs: The role of immune cells in severe acute pancreatitis and acute lung injury

From pancreas to lungs: The role of immune cells in severe acute pancreatitis and acute lung injury

Unraveling molecular and clinical aspects of ALKBH5 as dual role in colorectal cancer

m ⁶ A demethylase CpALKBH regulates CpZap1 mRNA stability to modulate the development and virulence of chestnut blight fungus

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ALKBH5 regulates arginase 1 expression in MDSCs and their immunosuppressive activity in tumor-bearing host

Cited by 4 publications

References 36 publications

From pancreas to lungs: The role of immune cells in severe acute pancreatitis and acute lung injury

From pancreas to lungs: The role of immune cells in severe acute pancreatitis and acute lung injury

Unraveling molecular and clinical aspects of ALKBH5 as dual role in colorectal cancer

m 6 A demethylase CpALKBH regulates CpZap1 mRNA stability to modulate the development and virulence of chestnut blight fungus

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m ⁶ A demethylase CpALKBH regulates CpZap1 mRNA stability to modulate the development and virulence of chestnut blight fungus