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circRNA-CPA4 Regulates Cell Proliferation and Apoptosis of Non-small Cell Lung Cancer via the miR-1183/PDPK1 Axis

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Abstract

Non-small-cell lung cancer (NSCLC) stands as a prevalent subtype of lung cancer, with circular RNAs emerging as key players in cancer development. This study elucidates the role of circRNA-CPA4 in NSCLC. Elevated circRNA-CPA4 expression in NSCLC lines was confirmed through qRT-PCR. Silencing circRNA-CPA4 with shRNA revealed, through CCK-8, colony formation, and flow cytometry assays, a notable constraint on proliferation and promotion of apoptosis in NSCLC cells. Subcellular localization analysis, RNA immunoprecipitation, and expression level assessments were employed to decipher the intricate interplay among miR-1183, circRNA-CPA4, and PDPK1. Results demonstrated heightened circRNA-CPA4 levels in NSCLC, and its knockdown curtailed NSCLC growth in vivo. Acting as a molecular sponge for miR-1183, circRNA-CPA4 regulated PDPK1 expression. Conversely, inhibiting miR-1183 counteracted the impact of circRNA-CPA4 silencing, reinstating NSCLC cell proliferation, and impeding apoptosis. Overall, this study unveils a novel mechanism: circRNA-CPA4 promotes PDPK1 expression by sequestering miR-1183, fostering NSCLC cell proliferation, and hindering apoptosis.

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Data Availability

The data supporting this study’s findings are available from the corresponding author upon reasonable request, fostering transparency, and facilitating further scientific inquiry.

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Acknowledgements

We express our gratitude for the unwavering efforts and dedication of every member involved in this study.

Funding

The study was funded by Yunnan Provincial Department of Science and Technology-Kunming Medical University Basic Research Joint Special Key Project, Grant/Award Number: 202201AY070001-136.

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Authors

Contributions

Conceptualization: HL, YL, GG; Data curation: HL, YL, NC, YH; Funding acquisition: YH; Methodology: HL, GG, XX; Validation: HL, YL, NC; Writing- original draft: HL; Writing—review & editing: HL, YL, NC, GG, XX, YH.

Corresponding author

Correspondence to Yunchao Huang.

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The authors declare no competing interests.

Ethical Approval

All animal experiments were performed in compliance with the guidelines established by the Animal Ethics of The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center) (Approval number: 2022-076, Date: 2022.8.13). The procedures followed the regulations outlined in the Guide for the Care and Use of Laboratory Animals (Jones-Bolin 2012).

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Li, H., Lei, Y., Chen, N. et al. circRNA-CPA4 Regulates Cell Proliferation and Apoptosis of Non-small Cell Lung Cancer via the miR-1183/PDPK1 Axis. Biochem Genet (2024). https://doi.org/10.1007/s10528-023-10641-0

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