Evidence map›Paper›PMID 41960367›Full record

ArticleHuman mutation2026

SIRT3 Regulates HMGCS2 Deacetylation and Influences Cholangiocarcinoma Progression via the Metabolism of Ketone Bodies.

Sihua Liu, Xiao You, Dongdong Wang, Xin Wang, Yuhang Yang, Fangfang Chen, Juan Zheng, Feiyu Qi, Wanliang Sun, Wei Peng and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human mutation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

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

13 authors.

Sihua LiuDepartment of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China, bbmc.edu.cn.
Xiao YouDepartment of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China, bbmc.edu.cn.
Dongdong WangDepartment of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China, bbmc.edu.cn.
Xin WangDepartment of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China, bbmc.edu.cn.
Yuhang YangDepartment of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China, bbmc.edu.cn.
Fangfang ChenDepartment of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China, bbmc.edu.cn.
Juan ZhengAnhui Key Laboratory of Tissue Transplantation, Bengbu Medical University, Bengbu, Anhui, China, bbmc.edu.cn.
Feiyu QiDepartment of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China, bbmc.edu.cn.
Wanliang SunDepartment of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China, bbmc.edu.cn.
Wei PengDepartment of General Surgery, The Hospital of Fengyang County, Chuzhou, China.
Jin XiAnhui Key Laboratory of Tissue Transplantation, Bengbu Medical University, Bengbu, Anhui, China, bbmc.edu.cn.
Zheng LuDepartment of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China, bbmc.edu.cn.ORCID https://orcid.org/0000-0002-8248-3426
Dengyong ZhangDepartment of General Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China, bbmc.edu.cn.ORCID https://orcid.org/0000-0003-4408-3357

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cholangiocarcinoma (CCA) is a highly aggressive malignancy. 3-Hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a mitochondrial enzyme involved in ketogenesis, has been linked to tumor progression, but its role in CCA remains unclear. HMGCS2 expression in CCA tissues was analyzed using TCGA data and immunoblotting (IB). Functional assays were performed in CCA cell lines (HuCCT-1 and RBE) and an in vivo xenograft model. Metabolomics explored HMGCS2-mediated metabolic changes. SIRT3-HMGCS2 interactions were examined via molecular docking, IF, CO-IP, GST pull-down, and CHX assays, with mutational analysis identifying interaction sites. IHC assessed clinical samples. HMGCS2 was downregulated in CCA. Overexpression inhibited proliferation and invasion, while knockdown promoted these effects, consistent in vitro and in vivo. Metabolomics showed HMGCS2 enhanced ketone body synthesis, and exogenous ketone bodies mimicked its antitumor effects. SIRT3 deacetylated HMGCS2 at K310 (with plasmid mutation assay), and low HMGCS2/SIRT3 expression correlated with poor patient survival. SIRT3-mediated deacetylation of HMGCS2 promotes ketone body synthesis, suppressing CCA progression. HMGCS2 is a potential therapeutic target for CCA.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaHydroxymethylglutaryl-CoA SynthaseKetone BodiesSirtuin 3AcetylationAnimalsCell Line, TumorCell ProliferationDisease ProgressionGene Expression Regulation, NeoplasticHumansMetabolomicsMiceHMGCS2 protein, humanHydroxymethylglutaryl-CoA SynthaseKetone BodiesSIRT3 protein, humanSirtuin 3acetylationcholangiocarcinomaHMGCS2ketone bodiesmutationSIRT3

Identifiers

PMID41960367
PMCPMC13057430

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Registered trials

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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.