J Cancer 2021; 12(24):7277-7286. doi:10.7150/jca.60049 This issue

Research Paper

CPNE3 regulates the cell proliferation and apoptosis in human Glioblastoma via the activation of PI3K/AKT signaling pathway

Dainan Zhang1,2, Xiaoyin Wang3, Xi Wang1, Zemin Wang4, Shunchang Ma2, Chuanbao Zhang1,2,5, Shaomin Li3,4, Wang Jia1,2✉

1. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
2. Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
3. Henan Key Laboratory of Neurorestoratology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China.
4. Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
5. Chinese Glioma Genome Atlas Network (CGGA), Beijing, China.

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Citation:
Zhang D, Wang X, Wang X, Wang Z, Ma S, Zhang C, Li S, Jia W. CPNE3 regulates the cell proliferation and apoptosis in human Glioblastoma via the activation of PI3K/AKT signaling pathway. J Cancer 2021; 12(24):7277-7286. doi:10.7150/jca.60049. Available from https://www.jcancer.org/v12p7277.htm

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Abstract

Graphic abstract

Background: Even with decades of intensive study, the signaling regulative network of the progression of Glioblastoma (GBM) remains unclear, a deeper understanding of the molecular crosstalk with pathways in GBM is needed to identify new potential targets for treatment. Copine-3 (CPNE3) was a member of a Ga2+ -dependent phospholipid-binding protein and was reported to play a role in multiple cancers.

Methods: To investigate the expression of CPNE3 in GBM, we applied bioinformatic analysis and clinical samples validation. Then the functional validation of carried out in commercially available glioma cell lines and nude mice model. Also, the GSEA analysis was used to identify the relevant pathways. The role of activated pathway was further validated by pharmacology method.

Results: We found that CPNE3 was significantly up-regulated in GBM when compared with adjacent normal tissues, and the overexpression of CPNE3 promoted cell proliferation and inhibiting cell apoptosis in vitro and in vivo. Also, the principal protein markers of PI3K/AKT pathway were found to be phosphorylated by CPNE3 over-expression, and pathway inhibitor, LY294002, alleviated the cell proliferation enhancement induced by CPNE3 over-expression.

Conclusion: Our results showed that the expression of CPNE3 promotes cell proliferation by inhibiting cell apoptosis via activating PI3K/AKT pathway. Thereby enhancing the progression of GBM, which suggest that CPNE3 may play as a tumorigenesis gene may become a promising potential therapeutic target for human GBMs.

Keywords: GBM, CPNE3, PI3K/AKT, cell proliferation, cell apoptosis