Identification of CDKN1A as a potential key risk factor in MASLD progression
文献类型：期刊论文
| 作者 | Deng, Lijuan2,3; Deng, Jianxin1; Luo, Liping3,9; Yang, Hongjia3; Sun, Mengxue3; Gao, Yucheng3,9; Liu, Qing3; Ngowi, Ebenezeri Erasto3,5,8; Zhou, Yinghua3; Zhang, Rongrong6 |
| 刊名 | FASEB JOURNAL
 |
| 出版日期 | 2025-04-15 |
| 卷号 | 39期号:7页码:15 |
| 关键词 | biomarkers CDKN1A liver MASLD RNA-seq |
| ISSN号 | 0892-6638 |
| DOI | 10.1096/fj.202402942R |
| 通讯作者 | Liu, Xiaojun(xiaojunliu@ibms.pumc.edu.cn) ; Qiao, Aijun(qiaoaijun@simm.ac.cn) |
| 英文摘要 | Metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as non-alcoholic fatty liver disease (NAFLD), is recognized as a highly heterogeneous condition. The elusive mechanisms driving its progression contribute to the lack of reliable diagnostic markers and effective treatments. In this study, we first identified 52 differentially expressed genes (DEGs) in MASLD stage by analyzing two public datasets, GSE126848 and GSE135251, using the DESeq2 and edgeR packages. Subsequently, these DEGs were subjected to protein-protein interaction (PPI) network analysis, revealing the top 10 hub genes. By intersecting the top 10 hub genes with another public dataset GSE260222, we observed that CDKN1A was the sole gene consistently upregulated in the livers of MASLD patients across all analyses. The elevated protein expression of CDKN1A was further validated in the livers of MASLD patients compared to control subjects. Consistently, compared to their respective control groups, both CDKN1A mRNA and protein levels were dramatically increased in the livers of MASLD animal models, including high-fat diet (HFD) induced obese mice, leptin-deficient obese (ob/ob) mice and leptin receptor-deficient (db/db) mice, and in mouse primary hepatocytes treated with free fatty acids (FFA), respectively. Interestingly, we found that CDKN1A transcript levels were progressively and significantly increased with the severity of MASLD in four out of five datasets and positively correlated with both the NAFLD activity score (NAS) and fibrosis stage, two important clinicopathological features of MASLD. Collectively, our results illustrated that CDKN1A may serve as a promising biomarker and therapeutic target for MASLD; however, its role in the disease's pathology warrants further investigation. |
| WOS关键词 | SENESCENCE ; P21 |
| 资助项目 | MOST | National Natural Science Foundation of China (NSFC)[82270925] ; MOST | National Natural Science Foundation of China (NSFC)[82470892] ; National Natural Science Foundation of China[2019B090904008] ; High-level New R&D Institute of the Department of Science and Technology of Guangdong Province[2021B0909050003] ; High-level Innovative Research Institute of the Department of Science and Technology of Guangdong Province[CXTD2023009] ; Zhongshan Science and Technology Bureau[CIFMS2021-I2M-1-016] ; Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences[7242094] ; Beijing Natural Science Foundation[JCYJ20230807115123046] ; Shenzhen Science and Technology Program |
| WOS研究方向 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001463439300001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/316980]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Liu, Xiaojun; Qiao, Aijun |
| 作者单位 | 1.Shenzhen Univ, Affiliated Hosp 1, Shenzhen Clin Res Ctr Metab Dis, Shenzhen Ctr Diabet Control & Prevent,Shenzhen Peo, Shenzhen, Guangdong, Peoples R China 2.Southern Med Univ, Sch Pharmaceut Sci, Guangzhou, Guangdong, Peoples R China 3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Guangdong, Peoples R China 4.Chinese Acad Med Sci, Inst Basic Med Sci, Dept Biochem & Mol Biol, State Key Lab Common Mech Res Major Dis, Beijing 100005, Peoples R China 5.Univ Chinese Acad Sci, Beijing, Peoples R China 6.Shenzhen Second Peoples Hosp, Dept Pathol, Shenzhen, Guangdong, Peoples R China 7.Peking Union Med Coll, Sch Basic Med, Beijing 100005, Peoples R China 8.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 9.Zunyi Med Univ, Sch Pharm, Zhuhai, Guangdong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Deng, Lijuan,Deng, Jianxin,Luo, Liping,et al. Identification of CDKN1A as a potential key risk factor in MASLD progression[J]. FASEB JOURNAL,2025,39(7):15. |
| APA | Deng, Lijuan.,Deng, Jianxin.,Luo, Liping.,Yang, Hongjia.,Sun, Mengxue.,...&Qiao, Aijun.(2025).Identification of CDKN1A as a potential key risk factor in MASLD progression.FASEB JOURNAL,39(7),15. |
| MLA | Deng, Lijuan,et al."Identification of CDKN1A as a potential key risk factor in MASLD progression".FASEB JOURNAL 39.7(2025):15. |
入库方式： OAI收割
来源：上海药物研究所
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