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SNRPB-mediated regulation of DDX39A splicing promotes ovarian cancer progression by regulating α6 integrin subunit expression

  • 0Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Shandong Key Laboratory of Reproductive Health and Birth Defects Prevention and Control, Ji'nan, Shandong Province, China. sduliyingwei@126.com.
Oncogene +

|

April 11, 2025

|

April 11, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study identifies DDX39A as a key regulator in ovarian cancer progression. Its dysregulation, influenced by SNRPB, promotes cancer cell proliferation and metastasis, offering a potential therapeutic target.

Area Of Science

  • Oncology
  • Molecular Biology
  • RNA Biology

Background

  • DEAD-box RNA helicases are implicated in cancer, but their specific roles in ovarian cancer remain unclear.
  • Understanding the regulatory mechanisms of these helicases is crucial for identifying therapeutic targets in ovarian cancer.

Purpose Of The Study

  • To identify key RNA helicases involved in ovarian cancer.
  • To elucidate the molecular mechanisms by which DDX39A contributes to ovarian cancer progression.
  • To investigate the regulatory relationship between SNRPB and DDX39A in ovarian cancer.

Main Methods

  • Systematic analysis of RNA helicase expression profiles using CPTAC and TCGA ovarian cancer datasets.
  • In vitro and in vivo functional studies including gene silencing (antisense oligonucleotides) and cell line models (CDX, PDX).
  • RNA sequencing (RNA-Seq) to analyze gene expression and alternative splicing events.

Main Results

  • DDX39A was identified as a significantly upregulated gene in ovarian cancer, associated with poor patient survival.
  • DDX39A silencing reduced tumor proliferation and metastasis in preclinical models.
  • SNRPB regulates DDX39A expression through intron retention, leading to noncoding transcript formation and reduced protein levels.
  • DDX39A promotes ovarian cancer progression by inducing exon skipping of ITGA6, generating the oncogenic ITGA6A transcript.

Conclusions

  • The SNRPB/DDX39A/ITGA6 axis is a critical driver of ovarian cancer progression.
  • DDX39A acts as an oncogene in ovarian cancer, mediating the effects of SNRPB.
  • DDX39A represents a promising therapeutic target for ovarian cancer treatment.

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