BMI1 Overexpression Alleviates Metabolic Syndrome‐Related Liver Injury by Inhibiting the Activation of the METTL3/AHNAK Axis
- 1Department of General Medicine Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai People's Republic of China
Abstract
Abnormal protein levels have been demonstrated to contribute to the progression of various diseases, including metabolic syndrome (MetS). Here, we speculated that the downregulation of BMI1 might lead to the failure of METTL3 degradation and contribute to METTL3 overexpression in MetS‐related liver injury. Rats were fed a diet consisting of a high proportion of fat and fructose (HFHF), and genetic intervention was performed via tail vein injection of liver‐specific AAV vectors. In the liver tissue of rats induced by HFHF, BMI1 was downregulated, while METTL3 and AHNAK were upregulated. BMI1 overexpression suppressed HOMA‐IR levels, downregulated the serum levels of TC, TG, ALT, and AST, and reduced oxidative stress‐related markers and the number of lipid droplets in liver tissues in rats with HFHF. BMI1 overexpression promoted the ubiquitination and degradation of METTL3 in BRL 3A cells, while METTL3 overexpression enhanced the m6A modification of AHNAK, leading to upregulation of AHNAK. Overexpression of METTL3 or AHNAK attenuated the mitigating effect of BMI1 overexpression in vivo and in vitro by activating the TGF‐β/SMAD signaling. These findings suggest that BMI1 overexpression alleviates MetS‐associated liver injury by inhibiting AHNAK m6A methylation through promoting METTL3 degradation, thereby suppressing the TGF‐β/SMAD signaling.
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BibTeX
@article{chen2026bmi1,
title = {{BMI1 Overexpression Alleviates Metabolic Syndrome‐Related Liver Injury by Inhibiting the Activation of the METTL3/AHNAK Axis}},
author = {Yun‐Jiang Chen and Bei Song and Kai‐Yu Cai and Yue‐Ling Du and Yan‐Chun Gong},
journal = {The Kaohsiung Journal of Medical Sciences},
year = {2026},
month = oct,
doi = {10.1002/kjm2.70308},
url = {https://doi.org/10.1002/kjm2.70308},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - BMI1 Overexpression Alleviates Metabolic Syndrome‐Related Liver Injury by Inhibiting the Activation of the METTL3/AHNAK Axis
AU - Yun‐Jiang Chen
AU - Bei Song
AU - Kai‐Yu Cai
AU - Yue‐Ling Du
AU - Yan‐Chun Gong
PY - 2026
DA - 2026/10/26
JO - The Kaohsiung Journal of Medical Sciences
DO - 10.1002/kjm2.70308
UR - https://doi.org/10.1002/kjm2.70308
AB - Abnormal protein levels have been demonstrated to contribute to the progression of various diseases, including metabolic syndrome (MetS). Here, we speculated that the downregulation of BMI1 might lead to the failure of METTL3 degradation and contribute to METTL3 overexpression in MetS‐related liver injury. Rats were fed a diet consisting of a high proportion of fat and fructose (HFHF), and genetic intervention was performed via tail vein injection of liver‐specific AAV vectors. In the liver tissue of rats induced by HFHF, BMI1 was downregulated, while METTL3 and AHNAK were upregulated. BMI1 overexpression suppressed HOMA‐IR levels, downregulated the serum levels of TC, TG, ALT, and AST, and reduced oxidative stress‐related markers and the number of lipid droplets in liver tissues in rats with HFHF. BMI1 overexpression promoted the ubiquitination and degradation of METTL3 in BRL 3A cells, while METTL3 overexpression enhanced the m6A modification of AHNAK, leading to upregulation of AHNAK. Overexpression of METTL3 or AHNAK attenuated the mitigating effect of BMI1 overexpression in vivo and in vitro by activating the TGF‐β/SMAD signaling. These findings suggest that BMI1 overexpression alleviates MetS‐associated liver injury by inhibiting AHNAK m6A methylation through promoting METTL3 degradation, thereby suppressing the TGF‐β/SMAD signaling.
SN - 1607-551X
SN - 2410-8650
ER -