Transposable elements alter gene expression and may impact response to cisplatin therapy in ovarian cancer

Daniela Moreira Mombach1, Rafael Luiz Vieira Mercuri2,3, Tiago Minuzzi Freire da Fontoura Gomes1

  • 1Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

Carcinogenesis
|May 9, 2024
PubMed

Insights

Transposable elements (TEs) like LINE1 and Alu are altered by cisplatin treatment in ovarian cancer cells. These TEs influence cancer genes and pathways, impacting drug resistance.

Area of Science:

  • Genomics
  • Cancer Biology
  • Molecular Oncology

Background:

  • Cisplatin is a cornerstone chemotherapy drug, but understanding cancer's resistance mechanisms is crucial for improving patient outcomes.
  • While gene expression changes are studied, the role of transposable elements (TEs) in cisplatin resistance remains underexplored.

Purpose of the Study:

  • To comprehensively investigate the expression and functional impact of transposable elements (TEs) in cisplatin-resistant ovarian cancer.
  • To elucidate how TEs influence host gene expression and cellular pathways in response to cisplatin therapy.

Main Methods:

  • Utilized RNA-sequencing (RNA-seq) and ATAC-sequencing (ATAC-seq) to compare cisplatin-sensitive and -resistant ovarian cancer cell lines.
  • Performed in-depth bioinformatics analysis to identify altered TEs and their interactions with host genes.

Main Results:

  • Cisplatin treatment significantly altered the expression of key TEs (LINE1, Alu, endogenous retroviruses) in both sensitive and resistant cell lines.
  • TEs were found to co-express with or form chimeric transcripts with host genes, potentially regulating tumor-related genes.
  • A model was developed demonstrating TEs influencing cancer genes and pathways critical for cisplatin response.

Conclusions:

  • Transposable element alterations are a significant consequence of cisplatin treatment, affecting critical cancer genes and pathways.
  • Considering the full spectrum of genomic elements, particularly TEs, is essential for a complete understanding of cancer treatment response and resistance.

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