2. Academic Validation
  3. Unraveling the mechanisms of RECQL4-mediated cervical cancer progression through the PI3K/AKT pathway

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

  • Transl Oncol. 2024 Dec:50:102146. doi: 10.1016/j.tranon.2024.102146.
Wen Huo 1,  Yiheng Huang 2,  Baoqinq Tian 2,  Xiaozheng Chen 2,  Jie Lu 2,  Xinyi Huang 2,  Meng Wu 2,  Jinming Yu 3,  Dawei Chen 4,  Ruozheng Wang 5
Affiliations

Affiliations

  • 1 Department of Radiation Oncology, Affiliated Tumor Hospital of Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, China.
  • 2 Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
  • 3 Department of Radiation Oncology, Affiliated Tumor Hospital of Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, China; Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address: sdyujinming@163.com.
  • 4 Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address: dave0505@yeah.net.
  • 5 Department of Radiation Oncology, Affiliated Tumor Hospital of Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, China. Electronic address: wrz8526@vip.163.com.
PMID: 39378549 DOI: 10.1016/j.tranon.2024.102146
Abstract

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.

Keywords

Cervical cancer; DNA damage; Genetic defects in tumours; RECQL4; Tumor proliferation.

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