Evidence map›Paper›PMID 38263056›Full record

ArticleJournal of translational medicine2024

Hypoxia upregulating ACSS2 enhances lipid metabolism reprogramming through HMGCS1 mediated PI3K/AKT/mTOR pathway to promote the progression of pancreatic neuroendocrine neoplasms.

Danyang Gu, Mujie Ye, Guoqin Zhu, Jianan Bai, Jinhao Chen, Lijun Yan, Ping Yu, Feiyu Lu, Chunhua Hu, Yuan Zhong and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
11.0field-weighted citation impact, top 1% of its field
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

31 citing papers in PubMed, 39 citations in OpenAlex.

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  20. Metabolic changes in neuroendocrine neoplasms.Cellular and molecular life sciences : CMLS · 2025
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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 at 3 institutions in 1 country.

Danyang Gu *Department of Geriatric Gastroenterology, Institute of Neuroendocrine Tumor, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China.
Mujie Ye *Department of Geriatric Gastroenterology, Institute of Neuroendocrine Tumor, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China.
Guoqin Zhu *Department of Geriatric Gastroenterology, Institute of Neuroendocrine Tumor, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China.
Jianan BaiDepartment of Geriatric Gastroenterology, Institute of Neuroendocrine Tumor, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China.
Jinhao ChenDepartment of Geriatric Gastroenterology, Institute of Neuroendocrine Tumor, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China.
Lijun YanDepartment of Geriatric Gastroenterology, Institute of Neuroendocrine Tumor, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China.
Ping YuDepartment of Geriatric Gastroenterology, Institute of Neuroendocrine Tumor, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China.
Feiyu LuDepartment of Geriatric Gastroenterology, Institute of Neuroendocrine Tumor, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China.
Chunhua HuDepartment of Geriatric Gastroenterology, Institute of Neuroendocrine Tumor, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China.
Yuan ZhongDepartment of Geriatric Gastroenterology, Institute of Neuroendocrine Tumor, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China.
Pengfei LiuDepartment of Gastroenterology, Jiangyin People's Hospital, Jiangsu, China. pengfeimd@163.com.
Qibin HeDepartment of Gastroenterology, The Affiliated Jiangning Hospital of Nanjing Medical University, Jiangsu, China. 496616814@qq.com.
Qiyun TangDepartment of Geriatric Gastroenterology, Institute of Neuroendocrine Tumor, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China. qytang@njmu.edu.cn.
Jiangsu Province Hospital · CNNanjing Medical University · CNJiangyin People's Hospital · CN

Funding

National Natural Science Foundation of China 82373180New Clinical TreatmentTechnology Research Fund BE2019753 (ZC19)Science Foundation Project of Ili & Jiangsu Joint Institute of Health yl2020lhms05Wuxi"Taihu talent plan" for the excellent medical expert team 2021-9
6 · The paper itself

Abstract

backgroundPancreatic neuroendocrine neoplasms (pNENs) are relatively rare. Hypoxia and lipid metabolism-related gene acetyl-CoA synthetase 2 (ACSS2) is involved in tumor progression, but its role in pNENs is not revealed. This study showed that hypoxia can upregulate ACSS2, which plays an important role in the occurrence and development of pNENs through lipid metabolism reprogramming. However, the precise role and mechanisms of ACSS2 in pNENs remain unknown.

methodsmRNA and protein levels of ACSS2 and 3-hydroxy-3-methylglutaryl-CoA synthase1 (HMGCS1) were detected using quantitative real-time PCR (qRT-PCR) and Western blotting (WB). The effects of ACSS2 and HMGCS1 on cell proliferation were examined using CCK-8, colony formation assay and EdU assay, and their effects on cell migration and invasion were examined using transwell assay. The interaction between ACSS2 and HMGCS1 was verified by Co-immunoprecipitation (Co-IP) experiments, and the functions of ACSS2 and HMGCS1 in vivo were determined by nude mouse xenografts.

resultsWe demonstrated that hypoxia can upregulate ACSS2 while hypoxia also promoted the progression of pNENs. ACSS2 was significantly upregulated in pNENs, and overexpression of ACSS2 promoted the progression of pNENs and knockdown of ACSS2 and ACSS2 inhibitor (ACSS2i) treatment inhibited the progression of pNENs. ACSS2 regulated lipid reprogramming and the PI3K/AKT/mTOR pathway in pNENs, and ACSS2 regulated lipid metabolism reprogramming through the PI3K/AKT/mTOR pathway. Co-IP experiments indicated that HMGCS1 interacted with ACSS2 in pNENs. Overexpression of HMGCS1 can reverse the enhanced lipid metabolism reprogramming and tumor-promoting effects of knockdown of ACSS2. Moreover, overexpression of HMGCS1 reversed the inhibitory effect of knockdown of ACSS2 on the PI3K/AKT/mTOR pathway.

conclusionOur study revealed that hypoxia can upregulate the lipid metabolism-related gene ACSS2, which plays a tumorigenic effect by regulating lipid metabolism through activating the PI3K/AKT/mTOR pathway. In addition, HMGCS1 can reverse the oncogenic effects of ACSS2, providing a new option for therapeutic strategy.

Indexed as

Lipid MetabolismPancreatic NeoplasmsAcetate-CoA LigaseAnimalsHumansHydroxymethylglutaryl-CoA SynthaseLipidsMetabolic ReprogrammingMicePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesAcetate-CoA LigaseACSS2 protein, humanHMGCS1 protein, humanHydroxymethylglutaryl-CoA SynthaseLipidsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesACSS2HMGCS1HypoxiaLipid metabolism reprogrammingPancreatic neuroendocrine neoplasmsPI3K/AKT/mTOR pathway

Identifiers

PMID38263056
PMCPMC10804556
OpenAlexW4391138487

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.