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Updated: Aug 8, 2026

Using the E1A Minigene Tool to Study mRNA Splicing Changes
10:25

Using the E1A Minigene Tool to Study mRNA Splicing Changes

Published on: April 22, 2021

Splicing factor HNRNPD and alternative splicing of MAP4K4 are associated with cell apoptosis and immune

Chunlei Yang1, Man Liao2, Haolun Xu1

  • 1Department of Urology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Plos One
|August 6, 2026
PubMed
Abstract

Insights

This study reveals a new HNRNPD-MAP4K4 splicing axis in Wilms' tumor, linking abnormal cell death to immune changes. This finding offers potential new biomarkers and therapies for this childhood kidney cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Wilms' tumor progression involves alternative splicing (AS), cell death imbalance, and immunosuppression.
  • The regulatory links between these factors in Wilms' tumor are not well understood.
  • This study constructs an "AS-cell death-immunity" network for Wilms' tumor.

Purpose of the Study:

  • To systematically construct and characterize a regulatory network connecting alternative splicing, cell death, and immunity in Wilms' tumor.
  • To identify key regulatory axes and their impact on the tumor microenvironment.
  • To provide a basis for novel therapeutic strategies.

Main Methods:

  • In silico analysis of RNA-seq data from Wilms' tumor and normal adjacent tissues (GSE138869).
  • Identification of cell death-related regulated alternative splicing events (RASEs) using the SUVA algorithm.
  • Construction of a tripartite regulatory network linking RASEs with differentially expressed splicing factors (DESFs) and immune cell infiltration (CIBERSORT).
  • Computational validation using HNRNPD knockout and FLASH-seq multi-omics data (GSE212767).

Main Results:

  • 118 cell death-related genes showed significant alternative splicing in Wilms' tumor.
  • A critical axis identified: overexpressed HNRNPD correlated with aberrant AS of MAP4K4 (clualt5p51764).
  • HNRNPD upregulation and MAP4K4 splicing shift correlated with increased monocyte infiltration.
  • Validation confirmed HNRNPD directly alters MAP4K4 splicing.

Conclusions:

  • The HNRNPD-MAP4K4 splicing axis connects apoptotic dysregulation to immune microenvironment remodeling in Wilms' tumor.
  • This computational framework generates hypotheses for novel prognostic biomarkers.
  • Findings support developing targeted therapies focused on the splicing machinery.

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