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Construction and identification of lncRNA/circRNA-coregulated ceRNA networks in gemcitabine-resistant bladder

Jingjing Pan1, Xiaojuan Xie2, Jinxiu Sheng1

  • 1Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University and the Key Clinical Laboratory of Henan Province, Zhengzhou, China.

Carcinogenesis
|October 3, 2023
PubMed
Abstract

Insights

Researchers uncovered regulatory networks involving long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) that drive chemoresistance in bladder cancer. These findings reveal key mechanisms and potential therapeutic targets for gemcitabine resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Chemoresistance is a major challenge in bladder cancer treatment.
  • Understanding the molecular mechanisms of chemoresistance is crucial for developing effective therapies.

Purpose of the Study:

  • To explore the regulatory networks underlying chemoresistance in bladder cancer.
  • To identify key long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) involved in gemcitabine resistance.

Main Methods:

  • Differential expression analysis of lncRNAs, circRNAs, miRNAs, and mRNAs in gemcitabine-resistant/sensitive bladder cancer cells using next-generation sequencing.
  • Bioinformatics analysis including chromosomal localization, classification, coexpression, and cis/trans regulation.
  • Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.
  • Construction of competing endogenous RNA (ceRNA) and protein-protein interaction networks.

Main Results:

  • Hundreds of differentially expressed lncRNAs and miRNAs, and thousands of circRNAs and mRNAs were identified.
  • Bioinformatics analysis revealed complex regulatory networks and functional roles of coregulated RNAs.
  • Specific examples include lncRNA LINP1 acting as a ceRNA for miR-193a-5p to increase TP73 expression, and lncRNA ESRG and hsa_circ_0075881 binding miR-324-3p to increase ST6GAL1 expression.
  • Modulation of ceRNA network components affected gemcitabine resistance in bladder cancer cells.

Conclusions:

  • Elucidated mechanisms of lncRNA and circRNA coregulation in bladder cancer gemcitabine resistance.
  • Established the foundation for identifying novel biomarkers and therapeutic targets for bladder cancer chemoresistance.

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