Evidence map›Paper›PMID 42210380›Full record

ArticleMolecular cancer2026

CircSPARC promotes esophageal squamous cell carcinoma through an HNRNPC-EPN2 splicing axis that activates Wnt/β-Catenin signaling.

Suli Dai, Cong Zhang, Zishuan Wei, Yaxin Liu, Yang Wen, Jinxia Chen, Xiaoya Li, Sisi Wei, Guogui Sun, Lianmei Zhao

Abstract read
In one paragraph

Article in Molecular cancer, 2026. 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. Review
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

10 authors.

Suli Dai *Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, China.
Cong Zhang *Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, China.
Zishuan WeiResearch Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, China.
Yaxin LiuResearch Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, China.
Yang WenResearch Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, China.
Jinxia ChenDepartment of Blood Transfusion, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, China.
Xiaoya LiResearch Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, China.
Sisi WeiResearch Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, China.
Guogui SunDepartment of Chemoradiotherapy, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei, 063000, China. sunguogui@ncst.edu.cn.
Lianmei ZhaoResearch Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, China. lianmei555@hebmu.edu.cn.

Funding

the Hebei Natural Science Foundation H2021206419the Hebei Provincial Government-funded Clinical Talent Project ZF2025178the National Natural Science Foundation of China 82303132the National Natural Science Foundation of China 82374090
6 · The paper itself

Abstract

backgroundPersistent activation of the Wnt/β-catenin signaling pathway is a key driver of esophageal squamous cell carcinoma (ESCC) progression. Circular RNAs (circRNAs) have emerged as critical regulators of oncogenic signaling in cancer. However, how circRNAs contribute to the sustained activation of Wnt/β-catenin signaling in ESCC is poorly defined.

methodsIntegrated analysis of self-sequenced and public circRNA datasets revealed elevated expression of circSPARC in ESCC. The functional effects of circSPARC on cell proliferation, migration, and invasion were evaluated through both in vitro and in vivo assays. RNA pull-down, RNA immunoprecipitation (RIP), alternative splicing analysis, RNA antisense purification (RAP), and cell surface protein biotinylation were used to elucidate the molecular mechanism by which circSPARC mediates aberrant Wnt/β-catenin activation in ESCC.

resultsThis study identifies a circRNA-mediated alternative splicing axis that promotes activation of Wnt/β-catenin signaling and ESCC progression. CircSPARC interacts with HNRNPC, a heterogeneous nuclear ribonucleoprotein involved in RNA processing, to suppress the tumor-suppressive long transcript of epsin 2 (EPN2), thereby impairing clathrin-mediated endocytosis-dependent degradation of the Wnt receptor frizzled 7 (FZD7). This interaction leads to sustained Wnt/β-catenin activation, thus promoting ESCC progression. Conversely, expression of the EPN2 long transcript restores circSPARC silencing-induced inhibition of Wnt/β-catenin signaling and suppresses ESCC cell malignancy both in vitro and in vivo. Clinically, elevated expression of circSPARC in ESCC tissues correlates with poor patient prognosis.

conclusionsThese findings reveal a circSPARC-HNRNPC-EPN2 axis that drives persistent Wnt/β-catenin activation through a mutation-independent mechanism. Targeting this pathway in tumors with high circSPARC expression presents a promising therapeutic strategy.

Indexed as

Esophageal NeoplasmsEsophageal Squamous Cell CarcinomaRNA, CircularWnt Signaling PathwayAlternative SplicingAnimalsbeta CateninCell Line, TumorCell MovementCell ProliferationGene Expression Regulation, NeoplasticHeterogeneous-Nuclear Ribonucleoprotein Group CHumansMicebeta CateninHeterogeneous-Nuclear Ribonucleoprotein Group CHNRNPC protein, humanRNA, CircularAlternative SplicingCircSPARCEsophageal Squamous Cell CarcinomaHNRNPCWnt/β-catenin

Identifiers

PMID42210380
PMCPMC13411977

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.