Evidence map›Paper›PMID 41770520›Full record

ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2026

A FOXO1-G6PC transcriptional axis restrains renal cell carcinoma progression: multi-omics, epigenetic, and mechanistic evidence.

Jieneng Wang, Bin Zhang, Hualan Ha, Xiaojun Zhang, Shujun Yang, Yao Luo, Yuelin Du, YuYuan He, WeiPing Li, Panfeng Shang

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Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Jieneng WangDepartment of Urology, Institute of Urology, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China.
Bin Zhang *Department of Urology Surgery, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan, 030012, Shanxi, China.
Hualan Ha *Department of Urology, Institute of Urology, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China.
Xiaojun ZhangDepartment of Urology, Institute of Urology, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China.
Shujun YangDepartment of Urology, Institute of Urology, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China.
Yao LuoDepartment of Urology, Institute of Urology, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China.
Yuelin DuDepartment of Urology, Institute of Urology, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China.
YuYuan HeDepartment of Anesthesiology and Operation Room, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China.
WeiPing LiDepartment of Urology Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China. liweipingmail@163.com.
Panfeng ShangDepartment of Urology, Institute of Urology, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China. shangpf@lzu.edu.cn.ORCID http://orcid.org/0000-0002-9622-9664

Funding

Natural Science Foundation of Gansu Province 21JR7RA379Natural Science Foundation of Gansu Province 22JR5RA964
6 · The paper itself

Abstract

backgroundG6PC has emerged as a prognostic biomarker and potential therapeutic target in cancer, but its role in renal cell carcinoma (RCC) remains unclear.

methodsWe analyzed G6PC expression using TCGA, GEO, and clinical data, with protein validation via HPA. Pathway enrichment, immune infiltration, and methylation analyses were performed. Prognostic value was assessed by Cox regression and Kaplan-Meier analysis. In vitro and in vivo experiments evaluated the effects of G6PC dysregulation. Transcriptome sequencing, ChIP-qPCR, and dual-luciferase reporter assays were used to identify upstream transcriptional regulators.

resultsG6PC was significantly downregulated in RCC and inversely correlated with TNM stage, grade, and immune infiltration. Hypomethylation of G6PC was observed. Enrichment analyses linked G6PC to BCR signaling and ECM-related pathways. Overexpression of G6PC inhibited RCC cell proliferation and migration. Mechanistically, FOXO1 was validated as a direct transcriptional regulator of G6PC, as demonstrated by enrichment of FOXO1 binding on the G6PC promoter (ChIP-qPCR) and promoter activation in dual-luciferase assays. Furthermore, G6PC exerted negative feedback on FOXO1 signaling, establishing a bidirectional regulatory loop.

conclusionsG6PC functions as a tumor suppressor in RCC and is directly transcriptionally activated by FOXO1, forming a FOXO1-G6PC axis that restrains RCC progression. This mechanistic insight highlights G6PC as a promising therapeutic and prognostic target.

Indexed as

Carcinoma, Renal CellForkhead Box Protein O1Kidney NeoplasmsAnimalsCell Line, TumorCell MovementCell ProliferationDisease ProgressionEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticHumansMaleMicePrognosisForkhead Box Protein O1FOXO1 protein, humanBiomarkerFOXO1G6PCImmune infiltrationPrognostic biomarkerRenal cell carcinoma

Identifiers

PMID41770520

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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.