Evidence map›Paper›PMID 40820012›Full record

ArticleScientific reports2025

Transcriptionally up-regulation of CDKN1A/p21 by TFE3 fusion proteins worsened TFE3-rearranged renal cell carcinoma.

Yanwen Lu, Wenliang Ma, Yi Chen, Xiang Dong, Xinghe Pan, Lei Yang, Shuoming Zhou, Ning Liu, Dongmei Li, Weidong Gan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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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

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0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Yanwen Lu *Department of Urology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, People's Republic of China.
Wenliang Ma *Department of Thoracic, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu, China.
Yi Chen *Department of Cardiology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, Jiangsu, China.
Xiang DongDepartment of Urology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, People's Republic of China.
Xinghe PanDepartment of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medical, Nanjing, Jiangsu, China.
Lei YangClinical and Translational Research Center, Department of Oncology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, Jiangsu, China.
Shuoming ZhouDepartment of Urology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, People's Republic of China.
Ning LiuDepartment of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210001, Jiangsu, China.
Dongmei LiState Key Laboratory of Analytical Chemistry for Life Science, Division of Anatomy and Histo-embryology, Medical School, Nanjing University, Nanjing, 210093, Jiangsu, China. lidm@nju.edu.cn.
Weidong GanDepartment of Urology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, People's Republic of China. gwd@nju.edu.cn.

Funding

Medical Research Project of Jiangsu Commission of Health ZD2022013Natural Science Foundation of Jiangsu Province No. BK20221444
6 · The paper itself

Abstract

The TFE3-rearranged renal cell carcinoma (TFE3-rRCC), which is an uncommon and aggressive form of kidney cancer, has an unfavorable prognosis. It has been shown that CDKN1A/p21 is high-expressed in TFE3-rRCC, however, the exact mechanism and the role of CDKN1A/p21 in TFE3-rRCC remain unclear. Our results indicated that the TFE3 fusions exacerbated TFE3-rRCC by transcriptionally upregulating CDKN1A/p21 expression. In terms of the mechanism, CDKN1A/p21 was a target gene of TFE3 fusions with positive regulation. Activation of AKT led to the cytoplasmic localization of highly expressed CDKN1A/p21, promoting TFE3-rRCC progression by anti-apoptosis and facilitating migration. Additionally, the remaining nuclear CDKN1A/p21 induced cellular senescence (CS) and secretion of senescence-associated secretory phenotype (SASP) factors, particularly IL-6 and IL-8, which recruited inhibitory immune cells and remodeled tumor microenvironment. This research presents that upregulation of CDKN1A/p21 transcriptionally by TFE3 fusions facilitates the progression of TFE3-rRCC by inducing anti-apoptosis, migration and CS, thus provides a promising target for treating TFE3-rRCC.

Indexed as

Basic Helix-Loop-Helix Leucine Zipper Transcription FactorsCarcinoma, Renal CellCyclin-Dependent Kinase Inhibitor p21Kidney NeoplasmsOncogene Proteins, FusionAnimalsApoptosisCell Line, TumorCell MovementCellular SenescenceGene Expression Regulation, NeoplasticHumansUp-RegulationBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCDKN1A protein, humanCyclin-Dependent Kinase Inhibitor p21Oncogene Proteins, FusionTFE3 protein, humanCDKN1A/p21Cellular senescenceSASPTFE3 fusionsTFE3-rRCC

Identifiers

PMID40820012
PMCPMC12358524

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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.