LNCHC directly binds and regulates YBX1 stability to ameliorate metabolic dysfunction-associated steatotic liver disease progression

doi:10.1111/liv.15975

科研成果详情

题名	LNCHC directly binds and regulates YBX1 stability to ameliorate metabolic dysfunction-associated steatotic liver disease progression
作者	Lu, Kaikai 1; Cheng, Xiaona 1; He, Lei 1,2; Li, Mengda 1; Chen, Qian 1; Qian, Chen 1; Zhao, Rong 1; Yang, Luyun 1; Liu, Fangtong 1; Liu, Sitong 1; Zhang, Tianyun 1; Feng, Lina 1; Wu, Litao 1; Wu, Xiaodan 1; Xu, Nan 3; Li, Ya 4; Wang, Jun 5; Han, Yu6; Yuan, Haiyang7,8; Liu, Tiemin 9; Zheng, Minghua7,8; Lu, Shemin 1; Li, Dongmin 1
发表日期	2024-06-07
发表期刊	Liver International 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	LNCHC MASLD PNPLA3 YBX1
其他关键词	DOMAIN-CONTAINING 3
摘要	Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the foremost cause of chronic liver disease, yet its underlying mechanisms remain elusive. Our group previously discovered a novel long non-coding RNA (lncRNA) in rats, termed lncHC and its human counterpart, LNCHC. This study aimed to explore the role of LNCHC in the progression of MASLD. Methods: RNA-binding proteins bound to LNCHC were searched by mass spectrometry. The target genes of LNCHC and Y-Box binding protein 1 (YBX1) were identified by RNA-seq. MASLD animal models were utilised to examine the roles of LNCHC, YBX1 and patatin-like phospholipase domain containing 3 (PNPLA3) in MASLD progression. Results: Here, we identified LNCHC as a native restrainer during MASLD development. Notably, LNCHC directly binds YBX1 and prevents protein ubiquitination. Up-regulation of YBX1 then stabilises PNPLA3 mRNA to alleviate lipid accumulation in hepatocytes. Furthermore, both cell and animal studies demonstrate that LNCHC, YBX1 and PNPLA3 function to improve hepatocyte lipid accumulation and exacerbate metabolic dysfunction-associated steatohepatitis development. Conclusions: In summary, our findings unveil a novel LNCHC functionality in regulating YBX1 and PNPLA3 mRNA stability during MASLD development, providing new avenues in MASLD treatment.
资助项目	National Natural Science Foundation of China
出版者	WILEY
ISSN	1478-3223
EISSN	1478-3231
卷号	44 期号:9 页码:2396-2408
DOI	10.1111/liv.15975
页数	13
WOS类目	Gastroenterology & Hepatology
WOS研究方向	Gastroenterology & Hepatology
WOS记录号	WOS:001240996100001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	38847599
SCOPUSEID	2-s2.0-85195284954
通讯作者地址	[Zheng, Minghua]Wenzhou Med Univ, Affiliated Hosp 1, MAFLD Res Ctr, Dept Hepatol, Wenzhou 325000, Zhejiang, Peoples R China. ; [Liu, Tiemin]Fudan Univ, Sch Life Sci, Dept Endocrinol & Metab, Shanghai 200438, Peoples R China.
Scopus学科分类	Hepatology
SCOPUS_ID	SCOPUS_ID:85195284954
TOP期刊	TOP期刊
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/214600
专题	附属第一医院_胃肠外科附属第一医院
通讯作者	Liu, Tiemin; Zheng, Minghua; Lu, Shemin
作者单位	1.Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Biochem & Mol Biol, Xian, Shaan Xi, Peoples R China; 2.Peking Univ, Hosp 1, Inst Urol, Natl Urol Canc Ctr China,Dept Urol, Beijing, Peoples R China; 3.Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Clin Lab, Xian, Shaan Xi, Peoples R China; 4.Xian Peoples Hosp, Xian Hosp 4, Dept Clin Lab, Xian, Shaanxi, Peoples R China; 5.Xian Childrens Hosp, Dept Infect Dis 2, Xian, Peoples R China; 6.Wenzhou Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Wenzhou, Peoples R China; 7.Wenzhou Med Univ, Affiliated Hosp 1, MAFLD Res Ctr, Dept Hepatol, Wenzhou 325000, Zhejiang, Peoples R China; 8.Key Lab Diag & Treatment Dev Chron Liver Dis Zheji, Wenzhou, Peoples R China; 9.Fudan Univ, Sch Life Sci, Dept Endocrinol & Metab, Shanghai 200438, Peoples R China
通讯作者单位	附属第一医院
推荐引用方式 GB/T 7714	Lu, Kaikai,Cheng, Xiaona,He, Lei,et al. LNCHC directly binds and regulates YBX1 stability to ameliorate metabolic dysfunction-associated steatotic liver disease progression[J]. Liver International,2024,44(9):2396-2408.
APA	Lu, Kaikai., Cheng, Xiaona., He, Lei., Li, Mengda., Chen, Qian., ... & Li, Dongmin. (2024). LNCHC directly binds and regulates YBX1 stability to ameliorate metabolic dysfunction-associated steatotic liver disease progression. Liver International, 44(9), 2396-2408.
MLA	Lu, Kaikai,et al."LNCHC directly binds and regulates YBX1 stability to ameliorate metabolic dysfunction-associated steatotic liver disease progression".Liver International 44.9(2024):2396-2408.