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Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
UBE2M Identified by CRISPR Screening as a Key Regulator of Cisplatin-Induced Acute Kidney Injury via the p53 Pathway
Cheng Yuan1,2,3, Feng Chen4,5, Xueyun Gao4
1Department of Oncology, Yichang Central People's Hospital and The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, China.
Introduction:
Acute kidney injury caused by cisplatin (Cis-AKI) is a major limitation in its clinical use, primarily due to the lack of effective therapeutic targets to mitigate nephrotoxicity. Although several molecular pathways are involved in Cis-AKI, identifying reliable and actionable therapeutic targets has been challenging. Through a CRISPR-based genome-wide screening approach, UBE2M was identified as a novel gene involved in cellular survival during cisplatin-induced stress. However, its expression, biological function, and underlying mechanism in Cis-AKI have not been thoroughly investigated. This study aims to identify key therapeutic targets for Cis- AKI and investigate the role of UBE2M in this condition.
Methods:
A CRISPR-Cas9 genome-wide screening approach was employed to identify key genes involved in cisplatin-induced renal tubular epithelial cell injury. UBE2M, identified as a critical survival factor, was further investigated using both gain- and loss-of-function strategies to explore its biological function and underlying regulatory mechanisms in the Cis-AKI model.
Results:
CRISPR screening identified UBE2M as a key regulator of cellular survival in Cis-AKI, and subsequent validation experiments confirmed its suppression in cisplatin-induced renal injury models. UBE2M overexpression alleviated apoptosis and renal injury by reducing p53 activation. In contrast, UBE2M knockdown exacerbated these effects, leading to increased apoptosis and renal injury.
Discussion:
This study reveals that UBE2M is a critical regulator of cisplatin-induced renal tubular epithelial cell injury. By regulating the p53-mediated apoptotic pathway, UBE2M protects against Cis-AKI.
Conclusion:
UBE2M could serve as a novel therapeutic target for the prevention and treatment of cisplatin-induced nephrotoxicity.
Insights
UBE2M is a key survival factor protecting against cisplatin-induced acute kidney injury (Cis-AKI). Upregulating UBE2M alleviates kidney damage by inhibiting p53-mediated apoptosis, suggesting it as a therapeutic target.
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- Cisplatin-induced acute kidney injury (Cis-AKI) poses a significant clinical challenge due to limited therapeutic options.
- Identifying novel molecular targets for mitigating cisplatin nephrotoxicity is crucial.
Purpose of the Study:
- To identify key therapeutic targets for Cis-AKI.
- To investigate the role and mechanism of UBE2M in cisplatin-induced renal injury.
Main Methods:
- Utilized CRISPR-Cas9 genome-wide screening to identify genes involved in cisplatin-induced renal tubular epithelial cell injury.
- Employed gain- and loss-of-function strategies to analyze UBE2M's biological function in a Cis-AKI model.
Main Results:
- CRISPR screening identified UBE2M as a critical survival factor in Cis-AKI.
- UBE2M was found to be suppressed in cisplatin-induced renal injury models.
- Overexpression of UBE2M reduced apoptosis and renal injury by inhibiting p53 activation, while knockdown exacerbated these effects.
Conclusions:
- UBE2M is a critical regulator of cisplatin-induced renal tubular epithelial cell injury.
- UBE2M protects against Cis-AKI by modulating the p53-mediated apoptotic pathway.
- UBE2M represents a potential novel therapeutic target for preventing and treating cisplatin nephrotoxicity.
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