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Background <p>Cervical cancer (CC) poses a significant health risk for women. Our previous studies have found that IMPA2 is an oncogene in CC and is associated with apoptosis; however, the exact regulatory mechanism is not clear.</p> Methods <p>To further investigate the role of IMPA2 in apoptosis, cellular morphology was examined using electron microscopy, ROS levels were measured with DCFH-DA probes, and apoptosis-related proteins were analyzed by western blot to characterize the apoptosis induced by <i>IMPA2</i> knockdown. To gain a deeper understanding of the apoptotic mechanism of <i>IMPA2</i> knockdown in CC cells, multi-omics analysis was performed on protein and phosphoprotein profiles. Apoptosis assay, cell cycle assay, RT-PCR, and western blotting were subsequently used for validation.</p> Results <p>Cytological experiments confirmed that <i>IMPA2</i> knockdown enhances the expression of cleaved caspase-3, Bax, and Bak, downregulates Bcl-2, induces mitochondrial morphological alterations, facilitates cytochrome c release from mitochondria, and promotes apoptosis through ROS accumulation. Multi-omics analysis showed IMPA2 may regulate cell cycle and DNA replication via CDK1/CDK2, with <i>IMPA2</i> knockdown in CC cells inducing G2/M phase arrest, reducing P-CDK1, CDK1, and MYC expression, effects reversed by <i>MYC</i> overexpression. Meanwhile, the ROS scavenger NAC rescues MYC downregulation and its downstream effects to prevent apoptosis.</p> Conclusion <p>This study demonstrates that IMPA2 regulates CC cell cycle and apoptosis via the MYC/CDK1 pathway, with <i>IMPA2</i> knockdown downregulating MYC/CDK1 in a ROS-dependent manner to induce G2/M arrest and apoptosis.</p>

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Multi-omics analysis reveals that knockdown of IMPA2 induces apoptosis in cervical cancer cells through ROS/MYC/CDK1 signaling

  • 期刊论文

  • 发表日期：

    2025年12月22日

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  • Xinyi Wu,
  • Bingqi Wang,
  • Lei Liu,
  • Zhenni Chen,
  • Min Wang

摘要

Background

Cervical cancer (CC) poses a significant health risk for women. Our previous studies have found that IMPA2 is an oncogene in CC and is associated with apoptosis; however, the exact regulatory mechanism is not clear.

Methods

To further investigate the role of IMPA2 in apoptosis, cellular morphology was examined using electron microscopy, ROS levels were measured with DCFH-DA probes, and apoptosis-related proteins were analyzed by western blot to characterize the apoptosis induced by IMPA2 knockdown. To gain a deeper understanding of the apoptotic mechanism of IMPA2 knockdown in CC cells, multi-omics analysis was performed on protein and phosphoprotein profiles. Apoptosis assay, cell cycle assay, RT-PCR, and western blotting were subsequently used for validation.

Results

Cytological experiments confirmed that IMPA2 knockdown enhances the expression of cleaved caspase-3, Bax, and Bak, downregulates Bcl-2, induces mitochondrial morphological alterations, facilitates cytochrome c release from mitochondria, and promotes apoptosis through ROS accumulation. Multi-omics analysis showed IMPA2 may regulate cell cycle and DNA replication via CDK1/CDK2, with IMPA2 knockdown in CC cells inducing G2/M phase arrest, reducing P-CDK1, CDK1, and MYC expression, effects reversed by MYC overexpression. Meanwhile, the ROS scavenger NAC rescues MYC downregulation and its downstream effects to prevent apoptosis.

Conclusion

This study demonstrates that IMPA2 regulates CC cell cycle and apoptosis via the MYC/CDK1 pathway, with IMPA2 knockdown downregulating MYC/CDK1 in a ROS-dependent manner to induce G2/M arrest and apoptosis.