Evidence map›Paper›PMID 39837984›Full record

ArticleActa pharmacologica Sinica2025

Organoid modeling identifies USP3-AS1 as a novel promoter in colorectal cancer liver metastasis through increasing glucose-driven histone lactylation.

Jia-Min Zhou, Wei-Xing Dai, Ren-Jie Wang, Wei-Qi Xu, Zhen Xiang, Yi-Xiu Wang, Ti Zhang, Yi-Ming Zhao, Lu Wang, An-Rong Mao

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Article in Acta pharmacologica Sinica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Jia-Min Zhou *Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.
Wei-Xing Dai *Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Ren-Jie Wang *Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Wei-Qi XuDepartment of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.
Zhen XiangDepartment of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.
Yi-Xiu WangDepartment of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.
Ti ZhangDepartment of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.
Yi-Ming ZhaoDepartment of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.
Lu WangDepartment of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China. wangluzl@fudan.edu.cn.
An-Rong MaoDepartment of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China. 13020143060@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysregulation of long non-coding RNAs (lncRNAs) is common in colorectal cancer liver metastasis (CRLM). Emerging evidence links lncRNAs to multiple stages of metastasis from initial migration to colonization of distant organs. In this study we investigated the role of lncRNAs in metabolic reprogramming during CRLM using patient-derived organoid (PDO) models. We established five pairs of PDOs from primary tumors and matched liver metastatic lesions, followed by microarray analysis. We found that USP3-AS1 was significantly upregulated in CRLM-derived PDOs compared to primary tumors. High level of USP3-AS1 was positively associated with postoperative liver metastasis and negatively correlated with the prognosis of colorectal cancer (CRC) patients. Overexpression of USP3-AS1 significantly enhanced both sphere formation efficiency and liver metastasis in PDOs. Gene set enrichment analysis revealed that USP3-AS1 upregulation significantly enriched glycolysis and MYC signaling pathways. Metabolomics analysis confirmed that USP3-AS1 promoted glycolysis in PDOs, whereas glycolysis inhibition partially attenuated the effects of USP3-AS1 overexpression on PDO growth and liver metastasis. We revealed that USP3-AS1 stabilized MYC via post-translational deubiquitination, thereby promoting glycolysis. We demonstrated that USP3-AS1 increased the stability of USP3 mRNA, resulting in higher USP3 protein expression. The elevated USP3 protein then interacted with MYC and promoted its stability by deubiquitination. The USP3-AS1-MYC-glycolysis regulatory axis modulated liver metastasis by promoting H3K18 lactylation and CDC27 expression in CRC. In conclusion, USP3-AS1 is a novel promoter of CRLM by inducing histone lactylation.

Indexed as

Colorectal NeoplasmsGlucoseHistonesLiver NeoplasmsOrganoidsRNA, Long NoncodingUbiquitin-Specific ProteasesGene Expression Regulation, NeoplasticGlycolysisHumansGlucoseHistonesRNA, Long NoncodingUbiquitin-Specific ProteasesUSP3 protein, humancolorectal cancerliver metastasismetabolic reprogrammingMYCorganoid modelUSP3-AS1

Identifiers

PMID39837984
PMCPMC12032002

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.