Abstract
Glioma is one of the most aggressive malignancies and has a poor survival rate. G protein subunit gamma 12 (GNG12), a member of G protein family, has been reported to participate in cancer disorders. However, the role and functional mechanism of GNG12 in glioma are not fully understood. The expression of GNG12 mRNA and miR-876-5p was measured by qRT-PCR. The level of GNG12 protein was measured by western blot. Cell proliferation and cell migration were monitored by CCK-8 assay and wound healing assay. The role of GNG12 on tumorigenicity in vivo was determined by animal models. The interaction between GNG12 and miR-876-5p was validated by dual-luciferase reporter experiment. The phosphorylation levels of PI3K and AKT were monitored by western blot. The upregulated expression of GNG12 was identified in tumor tissues and cells of glioma. GNG12 knockdown inhibited glioma cell growth and migration, and slowed tumor development in vivo. Besides, GNG12 knockdown weakened the phosphorylation levels of PI3K and AKT. GNG12 was verified to be a target of miR-876-5p whose enrichment suppressed the expression and function of GNG12. MiR-876-5p repressed glioma cell proliferation, migration, and the activity of PI3K/AKT signaling by targeting GNG12. MiR-876-5p-targeted GNG12 contributes to the malignant development of glioma by increasing the PI3K/AKT signaling activity.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This work was supported by the 2019–2020 General Project of Health Commission of Hubei Province: Study on the Blocking Effect and Mechanism of Interleukin-33 on Tumor Immune Escape (grant number WJ2019M099).
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Conceptualization: Ling Li; Methodology: Qiuying Zhang, Leyong Yuan; Formal analysis and investigation: Yanlong Yang; Writing — original draft preparation: Xiaobo Wang; Writing — review and editing: Ling Li, Fangfang Liu; Funding acquisition: Mingshui Xie; Resources: Yang Liu; Supervision: Ling Li, Xiaobo Wang.
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The present study was approved by the Ethics Committee of Suizhou Hospital, Hubei University of Medicine (Suizhou, China). The processing of clinical tissue samples is in strict compliance with the ethical standards of the Declaration of Helsinki.
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Li, L., Zhang, Q., Yuan, L. et al. GNG12 Targeted by miR-876-5p Contributes to Glioma Progression Through the Activation of the PI3K/AKT Signaling Pathway. J Mol Neurosci 72, 441–450 (2022). https://doi.org/10.1007/s12031-021-01956-x
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DOI: https://doi.org/10.1007/s12031-021-01956-x