Abstract
Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor in various cancer types, including non-small cell lung cancer (NSCLC). Circular RNA (circRNA) has recently been proven to be strongly linked with cancer progression. Here, we aimed to investigate the biological relevance and clinical significance of circRNA derived from PTEN in NSCLC. We found that circ-PTEN (hsa_circ_0094342) was significantly decreased in NSCLC tissues and serum, which was attributed to the upregulation of RNA-binding protein DHX9. Low circ-PTEN was linked with malignant clinical features and poor outcome. Exogenous expression of circ-PTEN markedly inhibited NSCLC cell proliferation in vitro as well as retarded tumor growth in vivo. Circ-PTEN increased the expression of its host gene PTEN via acting as a sponge for miR-155 and miR-330-3p, leading to the inactivation of the carcinogenic PI3K/AKT signaling pathway. The xenograft tumor model also indicated the existence of circ-PTEN/miR-155/miR-330-3p/PTEN regulatory axis in vivo. Our data for the first time demonstrate that circ-PTEN functions as a tumor-inhibiting circRNA in NSCLC through post-transcriptionally regulating PTEN, hinting a promising diagnostic/prognostic biomarker as well as therapeutic target for NSCLC patients.
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This work was supported by Education Scientific Research Fund “Young Seedlings” Project of Liaoning Provincial Department (QN2019015) and 345 Talent Project.
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(I) Conception and design: HYZ; (II) administrative support: HYZ; (III) provision of study materials or patients: YW; (IV) collection and assembly of data: ZBW and JBL; (V) data analysis and interpretation: YW; (VI) manuscript writing: HYZ; (VII) final approval of manuscript: All authors.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Shengjing Hospital of China Medical University (No. 2018PS249K), and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All animals were handled in strict accordance with the “Guide for the Care and Use of Laboratory Animals” and the “Principles for the Utilization and Care of Vertebrate Animals”, and all animal work was approved by the Institutional Animal Care and Use Committee of Shengjing Hospital of China Medical University.
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Wang, Y., Wang, Z., Lu, J. et al. Circular RNA circ-PTEN elevates PTEN inhibiting the proliferation of non-small cell lung cancer cells. Human Cell 34, 1174–1184 (2021). https://doi.org/10.1007/s13577-021-00526-y
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DOI: https://doi.org/10.1007/s13577-021-00526-y