Single-cell and bulk transcriptome profiling reveals RNA-binding protein regulatory programs in cervical cancer

Abstract The aberrant expression of RNA binding proteins (RBPs) is linked to various diseases, including cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, the single-cell landscape of RBPs in CESC remains unclear. We analyzed single-cell data from 2 HPV + and 2 HPV- C...

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Main Authors: Shasha Yang, Jingjing Zeng, Yong Wang, Yudi Tan, Li Yu, Jinkong Wei, Yuying Wei, Yuxuan Jin, Junying Chen
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-14823-1
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author Shasha Yang
Jingjing Zeng
Yong Wang
Yudi Tan
Li Yu
Jinkong Wei
Yuying Wei
Yuxuan Jin
Junying Chen
author_facet Shasha Yang
Jingjing Zeng
Yong Wang
Yudi Tan
Li Yu
Jinkong Wei
Yuying Wei
Yuxuan Jin
Junying Chen
author_sort Shasha Yang
collection DOAJ
description Abstract The aberrant expression of RNA binding proteins (RBPs) is linked to various diseases, including cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, the single-cell landscape of RBPs in CESC remains unclear. We analyzed single-cell data from 2 HPV + and 2 HPV- CESC samples to assess cell subtype composition and differential gene expression. Meanwhile, based on 2,141 reported RBPs, the expression patterns of different cell type-specific RBPs were further investigated. SUVA software was used to perform differential alternative splicing analysis on the TCGA CESC data. Finally, we did a lot of follow-up work and immunohistochemical studies to understand the true expression of RBP and its correlation with CESC prognosis. We observed a significant increase in the proportion of epithelial cells in the HPV + sample. The expression of RBP exhibited heterogeneity between HPV + and HPV- samples, with epithelial cells demonstrating the most diverse composition of RBP-expressing cell clusters. Results indicated that RNA splicing events were strongly associated with CESC progression. Covariation analysis identified 4 RBPs (CSTB, TIPARP, NDRG1, and NDRG2) correlated with 25 RNA alternative splicing events. Immunohistochemical experiments revealed that TIPARP expression was down-regulated in HPV + cervical cancer(p = 0.033). And the prognostic model that includes all RBPs, stage, and treatments may has have certain practical guiding significance for patients with CESC. Our study indicates that RBPs display specific expression patterns across HPV + and HPV- CESC. The regulatory checkpoints of these RBPs may serve as potential markers and therapeutic targets for the detection of HPV + CESC.
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spelling doaj-art-3b6f363338eb4f5da3e6c945dce040482025-08-20T03:46:00ZengNature PortfolioScientific Reports2045-23222025-08-0115111510.1038/s41598-025-14823-1Single-cell and bulk transcriptome profiling reveals RNA-binding protein regulatory programs in cervical cancerShasha Yang0Jingjing Zeng1Yong Wang2Yudi Tan3Li Yu4Jinkong Wei5Yuying Wei6Yuxuan Jin7Junying Chen8Department of Obstetrics and Gynecology, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Pathology, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Obstetrics and Gynecology, First Affiliated Hospital of Guangxi Medical UniversityAbstract The aberrant expression of RNA binding proteins (RBPs) is linked to various diseases, including cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, the single-cell landscape of RBPs in CESC remains unclear. We analyzed single-cell data from 2 HPV + and 2 HPV- CESC samples to assess cell subtype composition and differential gene expression. Meanwhile, based on 2,141 reported RBPs, the expression patterns of different cell type-specific RBPs were further investigated. SUVA software was used to perform differential alternative splicing analysis on the TCGA CESC data. Finally, we did a lot of follow-up work and immunohistochemical studies to understand the true expression of RBP and its correlation with CESC prognosis. We observed a significant increase in the proportion of epithelial cells in the HPV + sample. The expression of RBP exhibited heterogeneity between HPV + and HPV- samples, with epithelial cells demonstrating the most diverse composition of RBP-expressing cell clusters. Results indicated that RNA splicing events were strongly associated with CESC progression. Covariation analysis identified 4 RBPs (CSTB, TIPARP, NDRG1, and NDRG2) correlated with 25 RNA alternative splicing events. Immunohistochemical experiments revealed that TIPARP expression was down-regulated in HPV + cervical cancer(p = 0.033). And the prognostic model that includes all RBPs, stage, and treatments may has have certain practical guiding significance for patients with CESC. Our study indicates that RBPs display specific expression patterns across HPV + and HPV- CESC. The regulatory checkpoints of these RBPs may serve as potential markers and therapeutic targets for the detection of HPV + CESC.https://doi.org/10.1038/s41598-025-14823-1Alternative splicingCervical cancerEpithelial cellRNA binding proteinsScRNA-seq
spellingShingle Shasha Yang
Jingjing Zeng
Yong Wang
Yudi Tan
Li Yu
Jinkong Wei
Yuying Wei
Yuxuan Jin
Junying Chen
Single-cell and bulk transcriptome profiling reveals RNA-binding protein regulatory programs in cervical cancer
Scientific Reports
Alternative splicing
Cervical cancer
Epithelial cell
RNA binding proteins
ScRNA-seq
title Single-cell and bulk transcriptome profiling reveals RNA-binding protein regulatory programs in cervical cancer
title_full Single-cell and bulk transcriptome profiling reveals RNA-binding protein regulatory programs in cervical cancer
title_fullStr Single-cell and bulk transcriptome profiling reveals RNA-binding protein regulatory programs in cervical cancer
title_full_unstemmed Single-cell and bulk transcriptome profiling reveals RNA-binding protein regulatory programs in cervical cancer
title_short Single-cell and bulk transcriptome profiling reveals RNA-binding protein regulatory programs in cervical cancer
title_sort single cell and bulk transcriptome profiling reveals rna binding protein regulatory programs in cervical cancer
topic Alternative splicing
Cervical cancer
Epithelial cell
RNA binding proteins
ScRNA-seq
url https://doi.org/10.1038/s41598-025-14823-1
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