Evidence map›Paper›PMID 40264052›Full record

ArticleBMC cancer2025

The impact of an RNA-binding protein group on regulating the RSPO-LGR4/5-ZNRF3/RNF43 module and the immune microenvironment in hepatocellular carcinoma.

Zhengyao Xie, Zhiyan Dai, Ziyao Liu, Yiqiang Chen, Shuting Huang, Siyuan Liu, Jingjing Li, Jie Shen

Abstract read
In one paragraph

Article in BMC cancer, 2025. 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

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Zhengyao Xie *Department of Precision Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, China.ORCID http://orcid.org/0000-0002-5380-8316
Zhiyan Dai *Department of Precision Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, China.
Ziyao Liu *Department of Precision Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, China.
Yiqiang ChenDepartment of Precision Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, China.
Shuting HuangDepartment of Precision Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, China.
Siyuan LiuDepartment of Precision Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, China. koro1210@163.com.
Jingjing LiDepartment of Precision Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, China. jijilee_82@163.com.
Jie ShenDepartment of Precision Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, China. shenjie2008nju@163.com.

Funding

Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University 2024-LCYJ-PY-59Medical New Technology Development Project of Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School XJSFZLX202321Project of The National Health Commission Health Development Research Center No. WKZX2023CX020001
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) is a leading cause of cancer mortality. RNA-binding proteins (RBPs) are potential therapeutic targets because of their role in tumor progression. This study investigated the interactions between specific HCC progression-associated RBPs (HPARBPs), namely, ILF3, PTBP1, U2AF2, NCBP2, RPS3, and SSB, in HCC and their downstream targets, as well as their impact on the immune microenvironment and their clinical value.

methodsTissue samples from human HCC, collected from 28 patients who experienced recurrence following postoperative adjuvant therapy were examined. The mRNA levels of RBPs and their prospective targets were quantified through RNA isolation and quantitative real-time PCR. Data from two public datasets were scrutinized for both expression and clinical relevance. Through Student's t test and logistic regression, HPARBPs were identified. Enhanced cross-linking immunoprecipitation (eCLIP) experiments revealed RBP-RNA interactions in HepG2 cells. For functional enrichment, Metascape was used, whereas CIBERSORT was used to characterize the immune microenvironment.

resultsPublic database analysis confirmed widespread RBP expression abnormalities in HCC (false discovery rate < 0.00001 and fold change ≥ 1.15 or ≤ 0.85), leading to the identification of 42 HPARBPs and core modules. eCLIP data analysis revealed the specificity of downstream target genes and binding site features for core HPARBPs (signal value > 3, P value < 0.01). Four core HPARBPs may bind to RNAs of genes in the RSPO-LGR4/5-ZNRF3/RNF43 module, affecting the Wnt pathway and HCC progression. Immunoinfiltration analysis revealed changes in the HCC immune microenvironment due to altered expression of relevant genes.

conclusionIn our study, we identified core HPARBPs that might contribute to HCC progression by binding to RNAs in the RSPO-LGR4/5-ZNRF3/RNF43 module. Changes in the expression of HPARBPs affect the HCC immune microenvironment. Our findings offer novel insights into the regulatory network of Wnt pathway-related RBPs and their potential clinical value in HCC.

Indexed as

Carcinoma, HepatocellularCCAAT-Enhancer-Binding ProteinsLiver NeoplasmsRNA-Binding ProteinsTumor MicroenvironmentUbiquitin-Protein LigasesDNA-Binding ProteinsFemaleGene Expression Regulation, NeoplasticHep G2 CellsHumansMaleMiddle AgedR-SpondinsThrombospondinsCCAAT-Enhancer-Binding ProteinsDNA-Binding ProteinsRNA-Binding ProteinsRNF43 protein, humanRspo2 protein, humanR-SpondinsThrombospondinsUbiquitin-Protein LigasesZNRF3 protein, humanEnhanced cross-linking immunoprecipitationHepatocellular carcinomaPosttranscriptional regulationRNA-binding proteinsTumor immune microenvironment

Identifiers

PMID40264052
PMCPMC12012940

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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.