Evidence map›Paper›PMID 38702028›Full record

ArticleJournal of advanced research2025

MIER2/PGC1A elicits sunitinib resistance via lipid metabolism in renal cell carcinoma.

Zhihao Wei, Yuzhong Ye, Chenchen Liu, Qi Wang, Yunxuan Zhang, Kailei Chen, Gong Cheng, Xiaoping Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
–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

21 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Identification of novel HIF2α inhibitors: a structure-based virtual screening approach.Journal of enzyme inhibition and medicinal chemistry · 2026
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  18. Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  19. The role of acetylation and deacetylation in cancer metabolism.Clinical and translational medicine · 2025
    Review
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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

8 authors.

Zhihao WeiDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yuzhong YeDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Chenchen LiuDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Qi WangDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yunxuan ZhangDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Kailei ChenDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Gong ChengDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: cg0178@qq.com.
Xiaoping ZhangDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Shenzhen Huazhong University of Science and Technology Research Institute, China. Electronic address: xzhang@hust.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionRenal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system and accounts for more than 90 % of all renal tumors. Resistance to targeted therapy has emerged as a pivotal factor that contributes to the progressive deterioration of patients with advanced RCC. Metabolic reprogramming is a hallmark of tumorigenesis and progression, with an increasing body of evidence indicating that abnormal lipid metabolism plays a crucial role in the advancement of renal clear cell carcinoma.

objectivesClarify the precise mechanisms underlying abnormal lipid metabolism and drug resistance.

methodsBioinformatics screening and analyses were performed to identify hub gene. qRT-PCR, western blot, chromatin immunoprecipitation (ChIP) assays, and other biological methods were used to explore and verify related pathways. Various cell line models and animal models were used to perform biological functional experiments.

resultsIn this study, we identified Mesoderm induction early response 2 (MIER2) as a novel biomarker for RCC, demonstrating its role in promoting malignancy and sunitinib resistance by influencing lipid metabolism in RCC. Mechanistically, MIER2 facilitated P53 deacetylation by binding to HDAC1. Acetylation modification augmented the DNA-binding stability and transcriptional function of P53, while deacetylation of P53 hindered the transcriptional process of PGC1A, leading to intracellular lipid accumulation in RCC. Furthermore, Trichostatin A (TSA), an inhibitor of HDAC1, was found to impede the MIER2/HDAC1/P53/PGC1A pathway, offering potential benefits for patients with sunitinib-resistant renal cell cancer.

conclusionOur findings highlight MIER2 as a key player in anchoring HDAC1 and inhibiting PGC1A expression through the deacetylation of P53, thereby inducing lipid accumulation in RCC and promoting drug resistance. Lipid-rich RCC cells compensate for energy production and sustain their own growth in a glycolysis-independent manner, evading the cytotoxic effects of targeted drugs and ultimately culminating in the development of drug resistance.

Indexed as

Carcinoma, Renal CellDrug Resistance, NeoplasmKidney NeoplasmsLipid MetabolismPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaSunitinibAnimalsAntineoplastic AgentsCell Line, TumorGene Expression Regulation, NeoplasticHistone Deacetylase 1HumansMiceTumor Suppressor Protein p53Antineoplastic AgentsHDAC1 protein, humanHistone Deacetylase 1Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPPARGC1A protein, humanSunitinibTumor Suppressor Protein p53Clear cell renal cell carcinomaDeacetylationLipid metabolismMIER2Sunitinib resistance

Identifiers

PMID38702028
PMCPMC11976417

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.