Evidence map›Paper›PMID 41103217›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

CircSMEK1 Suppresses HCC via the hnRNPK-IGF2-AKT Axis: A Diagnostic Biomarker and Therapeutic Target.

Peilan Guo, Xiaomeng Jia, Shenghong Wang, Xinyu Li, Yajing Liu, Lisen Lin, Zhengkun Wang, Fujun Liu, Slawomir Wolczynski, Nafis Rahman and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

16 authors.

Peilan GuoState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.ORCID https://orcid.org/0000-0002-6757-3650
Xiaomeng JiaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Shenghong WangState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Xinyu LiShandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, 250021, China.
Yajing LiuState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Lisen LinState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Zhengkun WangState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Fujun LiuYantai Yuhuangding Hospital Affiliated to Qingdao University, Shandong, 264000, China.
Slawomir WolczynskiDepartment of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Bialystok, 37801, Poland.
Nafis RahmanDepartment of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Bialystok, 37801, Poland.
Jie GaoYantai Yuhuangding Hospital Affiliated to Qingdao University, Shandong, 264000, China.
Xuguang DuState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Suk-Ying TsangSchool of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
Jiali LiuState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Wei SongShandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, 250021, China.
Xiangdong LiState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.ORCID https://orcid.org/0000-0003-2261-2393

Funding

2115 Talent Development Program of China Agricultural UniversityMedical University of Bialystok, Poland SUB/1/DN/21/003/1104National Natural Science Foundation of China 82171854
6 · The paper itself

Abstract

The mechanism underlying metabolic dysfunction-associated steatohepatitis (MASH) to hepatocellular carcinoma (HCC) is elusive, and whether circRNA can serve as biomarker or therapeutic target for MASH/HCC needs to be systematically explored. Integrative transcriptomic analysis of circRNA from MASH and HCC were performed. Multi-cohort analyses of serum and tissues from MASH and HCC patients (n = 206) were conducted. Mechanisms are explored via RNA-protein interaction assays, CRISPR-mediated knockdown, and xenograft/PiggyBac-mediated mice models. circSMEK1 is significantly decreased in MASH/HCC tissues and serum, correlating with tumor size, vascular invasion, and overall survival. Mechanistically, nuclear circSMEK1 binds hnRNPK, promoting its ubiquitin-mediated degradation, suppressing IGF2 transcription and PI3K/AKT signaling. Loss of circSMEK1 elevated autocrine IGF2 in HCC promoting tumor growth, also activated AKT in cancer-associated fibroblasts through paracrine, fostering an immunosuppressive microenvironment. SF3B4 overexpression drove circSMEK1 depletion in HCC. In murine models, circSMEK1 restoration inhibited tumor growth and metastasis. circSMEK1 is a tumor-suppressor in MASH/HCC through the hnRNPK-IGF2-AKT axis. The serum level of circSMEK1 has non-invasive diagnostic value for HCC (AUC = 0.790), as well as potential diagnostic utility for early HCC or high-risk MASH, owing to its key role in bridging MASH to HCC progression. Restoring of circSMEK1, alone or combined with IGF2 inhibitors, proposing a novel therapeutic strategy for HCC.

Indexed as

Carcinoma, HepatocellularHeterogeneous-Nuclear Ribonucleoprotein KInsulin-Like Growth Factor IILiver NeoplasmsProto-Oncogene Proteins c-aktRNA, CircularAnimalsBiomarkers, TumorCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMaleMiceSignal TransductionBiomarkers, TumorHeterogeneous-Nuclear Ribonucleoprotein KHNRNPK protein, humanIGF2 protein, humanInsulin-Like Growth Factor IIProto-Oncogene Proteins c-aktRNA, CircularcircRNAHCCIGF2MASLDserum biomarker

Identifiers

PMID41103217
PMCPMC12752665

What OpenQuestion holds

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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.