Evidence map›Paper›PMID 40640337›Full record

ArticleOncogene2025

The molecular axis hnRNPU/circKCNK2/EDC4/IL-11 aggravates osteolytic bone metastasis of RCC.

Yiqiu Wang, Ding Zhao, Jiayi Lu, Naiqiao Hou, Qianyun Wu, Sian Zhou, Junyao Xu, Wei Xue, Wenguo Cui, Junhua Zheng and 2 more

Abstract read
In one paragraph

Article in Oncogene, 2025. 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

12 authors.

Yiqiu Wang *Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ding Zhao *Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jiayi Lu *Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Naiqiao Hou *Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Qianyun WuDepartment of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Sian ZhouDepartment of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Junyao XuDepartment of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wei XueDepartment of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wenguo CuiDepartment of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Junhua ZhengDepartment of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. zhengjh0471@sina.com.
Fei WangDepartment of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wf11878@rjh.com.cn.
Wei ZhaiDepartment of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. jacky_zw2002@hotmail.com.ORCID http://orcid.org/0000-0001-6274-6404

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82173214
6 · The paper itself

Abstract

Bone metastasis, which is associated with adverse outcomes, is a serious health concern for renal cell carcinoma (RCC) patients, especially considering the limited therapeutic options. In this study, we investigated the expression profiling of circRNAs in five primary RCC samples and RCC-bone metastases (Bone Met) using high-throughput screening and identified an upregulated circRNA in Bone Met (hsa_circ_0016459, circKCNK2). Notably, overexpression of circKCNK2 could promote osteoclast differentiation and accelerate the destruction of osteolytic bone metastasis by stimulating IL-11 secretion. Additionally, we observed that RCC with a high circKCNK2 expression could benefit from an anti-IL-11 strategy rather than a denosumab-based therapeutic regimen. At the molecular level, circKCNK2 is competitively bound to EDC4 (a scaffold protein of P-bodies). The interaction between circKCNK2 and EDC4α-helical disrupted the combination of DCP1 and DCP2, which weakened the function of P-bodies and resulted in an increased level of IL-11 mRNA and finally activated STAT-3 signaling in osteoclast precursors (OPs). This axis could be blocked with a mutation of EDC4α-helical. Further experiments revealed that increased circKCNK2 production in bone metastases was attributed to decreasing expression of heterogeneous nuclear ribonucleoprotein U (hnRNPU) under an acidic microenvironment. Our findings suggest that circKCNK2 could have a critical role in linking P-bodies to IL-11/STAT-3 signaling. Developing a secure and effective gene delivery system targeted at circKCNK2 is promising for RCC therapy.

Indexed as

Bone NeoplasmsCarcinoma, Renal CellInterleukin-11Kidney NeoplasmsOsteolysisRNA, CircularAnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMaleMiceOsteoclastsSignal TransductionIL11 protein, humanInterleukin-11RNA, Circular

Identifiers

PMID40640337
PMCPMC12399430

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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.