1.Targeting ER lipid raft-associated 1 reveals a coordinated cholesterol-dependent vulnerability in hepatocellular carcinoma
Yiming ZHANG ; Yushan HOU ; Xinxin WANG ; Kaikun XU ; Pei JIANG ; Siqi WANG ; Huimin KANG ; Hu ZHANG ; Jingzhuo JIN ; Xiaofen HUANG ; Zifeng LIU ; Songpeng YANG ; Jiaqi LIU ; Lingqiang ZHANG ; Fuchu HE ; Chunyan TIAN ; Aihua SUN
Clinical and Molecular Hepatology 2026;32(2):866-883
Background/Aims:
Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed.
Methods:
We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models.
Results:
ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis.
Conclusions
ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.
2.Polymorphism study of six miniSTR loci in Han population from Northeast China
Wei MA ; Zhufeng ZHANG ; Jian SHEN ; Yan LI ; Zifeng PEI ; Fei XU
Chinese Journal of Tissue Engineering Research 2009;13(31):6181-6184
OBJECTIVE:Allele frequencies and forensic parameters for six miniSTR loci(D10S1248,D14S1434,D22S1045,D4S2364,D2S441 and D1S1677)were analyzed in a population of 173 unrelated Chinese Han population individuals from Northeast China.METHODS:The six miniSTR loci were preformed in two multiplex fluorescent PCR systems.ABI 310 Genetic Analyzer was utilized in capillary electrophoresis and the lengths of allele fragments were analyzed.Genetic data collection and analysis software were used for data collection and genotyping.Statistical analysis was performed to the data.RESULTS:The six miniSTR loci showed a moderate degree of polymorphism in Han population from Northeast China.The observed allele sizes were from 67 bp to 115 bp,and the observed heterozygosity ranged from 0.728 to 0.827.The combined power of discrimination and the combined power of exclusion for the six miniSTR loci in Northeast China were 0.999 99,and 0.993 31,respectively.CONCLUSION:The six miniSTR showed a moderate genetic polymorphism in Han population from northeast of China.Due to their small size of PCR amplicon,the six miniSTR could be useful supplements to the CODIS STRs,and they would be useful in population genetics and forensic analysis.

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