Deciphering STAT3’s negative regulation of LHPP in ESCC progression through single-cell transcriptomics analysis

Sep 21, 2026

Uploaded by Skyler

Background: Esophageal Squamous Cell Carcinoma (ESCC) has high prevalence and mortality, and its cellular and molecular complexity remains challenging. Single-cell transcriptomics enables resolution of tumor microenvironment heterogeneity. Objective: This study clarifies STAT3-driven transcriptional regulation of LHPP and its functional relevance to ESCC progression. Methods: Single-cell RNA sequencing profiled 44,206 cells from tumor and adjacent normal tissues, with differential expression, qPCR validation in 21 patients, and functional assays in ESCC cell lines.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Esophageal squamous cell carcinoma burden and prognosis

Single-cell transcriptomics versus bulk transcriptomics

Transcription factors and the role of STAT3

Chen et al. Molecular Medicine (2024) 30:192 [https://doi.org/10.1186/s10020-024-00962-0](https://doi.org/10.1186/s10020-024-00962-0) Molecular Medicine RESEARCH Open Access Deciphering STAT3’s negative regulation of LHPP in ESCC progression through single-cell transcriptomics analysis Yurao Chen1,2†, Zemao Zheng1,2†, Luoshai Wang3†, Ronghuai Chen1,2, Ming He1,2, Xiang Zhao1,2, Liyan Jin4,5* and Juan Yao1,2* Abstract Background Esophageal Squamous Cell Carcinoma (ESCC) remains a predominant health concern in the world, characterized by high prevalence and mortality rates. Advances in single-cell transcriptomics have revolutionized cancer research by enabling a precise dissection of cellular and molecular diversity within tumors. Objective This study aims to elucidate the cellular dynamics and molecular mechanisms in ESCC, focusing on the transcriptional influence of STAT3 (Signal Transducer and Activator of Transcription 3) and its interaction with LHPP, thereby uncovering potential therapeutic targets. Methods Single-cell RNA sequencing was employed to analyze 44,206 cells from tumor and adjacent normal tissues of ESCC patients, identifying distinct cell types and their transcriptional shifts. We conducted differential gene expression analysis to assess changes within the tumor microenvironment (TME) . Validation of key regulatory interactions was performed using qPCR in a cohort of 21 ESCC patients and further substantiated through experimental assaysin ESCC cell lines. Results The study revealed critical alterations in cell composition and gene expression across identified cell populations, with a notable shift towards pro-tumorigenic states. A significant regulatory influence of STAT3 on LHPP was discovered, establishing a novel aspect of ESCC pathogenesis. Elevated levels of STAT3 and suppressed LHPP expression were validated in clinical samples. Functional assays confirmed that STAT3 directly represses LHPP at the promoter level, and disruption of this interaction by promoter mutations diminished STAT3’s repressive effect. Conclusion This investigation underscores the central role of STAT3 as a regulator in ESCC, directly impacting LHPP expression and suggesting a regulatory loop crucial for tumor behavior. The insights gained from our comprehensive cellular and molecular analysis offer a deeper understanding of the dynamics within the ESCC microenvironment. These findings pave the way for targeted therapeutic interventions focusing on the STAT3-LHPP axis, providing a strategic approach to improve ESCC management and prognosis. Keywords ESCC, Single-cell transcriptomics, Tumor microenvironment, STAT3, LHPP †Yurao Chen, Zemao Zheng and Luoshai Wang have contributed equally to this work. *Correspondence: Liyan Jin [jinliyan@wjrmyy.cn](jinliyan@wjrmyy.cn)[ ](jinliyan@wjrmyy.cn)Juan Yao tzsry1 [10120@163.com](10120@163.com) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/.)[.](http://creativecommons.org/licenses/by/4.0/.) Chen et al. Molecular Medicine (2024) 30:

FAQs

What question does the study address about ESCC progression?

It investigates how STAT3 negatively regulates LHPP and how this transcriptional control contributes to ESCC progression through tumor microenvironment dynamics.

How were cellular changes in ESCC assessed?

Single-cell RNA sequencing analyzed 44,206 cells from tumor and adjacent normal tissues to identify cell types and transcriptional shifts, followed by differential expression analysis within the tumor microenvironment.

How was the STAT3–LHPP regulatory relationship validated?

Key regulatory interactions were validated using qPCR in a cohort of 21 ESCC patients and supported by experiments in ESCC cell lines.

Sep 21, 2026

Uploaded by Skyler