Translational Oncology (Dec 2024)

Unraveling the mechanisms of RECQL4-mediated cervical cancer progression through the PI3K/AKT pathway

  • Wen Huo,
  • Yiheng Huang,
  • Baoqinq Tian,
  • Xiaozheng Chen,
  • Jie Lu,
  • Xinyi Huang,
  • Meng Wu,
  • Jinming Yu,
  • Dawei Chen,
  • Ruozheng Wang

Journal volume & issue
Vol. 50
p. 102146

Abstract

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Background: RECQL4 is a member of the DNA helicase family and is critical for DNA replication, DNA damage repair, and tumor progression. However, its specific role in cervical cancer remains uncertain. Methods: In this study, we aimed to investigate the impact of RECQL4 on cervical cancer prognosis using clinical specimens from The Cancer Genome Atlas. We evaluated the malignant effects of RECQL4 through various experimental assays including cell Cell Counting Kit-8, EdU, colony formation, cell cycle analysis, cell apoptosis, scratch, and Transwell assays. We explored the mechanisms of RECQL4-regulated malignancy using analyses of bioinformatics, RNA sequencing data, polymerase chain reaction (PCR), western blotting, and cell immunofluorescence experiments. Furthermore, we validated the effects of RECQL4 knockdown on tumor growth using subcutaneous tumor models in nude mice. Results: RECQL4 was upregulated in cervical cancer and correlated with prognosis, demonstrating a positive relationship with tumor mutational burden. Knockdown of RECQL4 inhibits cervical cancer cell proliferation, migration, and invasion, suppresses epithelial-mesenchymal transition status, induces cell cycle arrest, and promotes apoptosis. Mechanistically, RECQL4 mediated malignancy through the PI3K/AKT pathway and reduced nuclear β-catenin expression. In vivo studies further confirmed that RECQL4 knockout significantly inhibited tumor growth. Conclusions: Our findings provide novel insights into the mechanism behind RECQL4-mediated cervical cancer progression through the PI3K/AKT pathway. Furthermore, our study suggests potential therapeutic strategies for targeting RECQL4 in cervical cancer treatment.

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