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GTF2E2 downregulated by miR-340-5p inhibits the malignant progression of glioblastoma

Cancer Gene Therapy volume 30, pages 1702–1714 (2023)Cite this article

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Abstract

Glioblastoma is the most common malignant tumor in the central nervous system. The general transcription factor IIE subunit beta (GTF2E2) is crucial for physiological and pathological functions, but its roles in the malignant biological function of glioma remain ambiguous. CCK-8, colony formation assays, TUNEL assays, cell migration assays, wound-healing assays, and xenograft model were established to investigate the biological functions of GTF2E2 both in vitro and in vivo. GTF2E2 was overexpressed in glioma and was associated with poor prognosis of glioma patients. Biological functions of GTF2E2 were investigated both in vitro and in vi0vo by multiple experiments. Moreover, we explored the possible mechanisms of GTF2E2. In our results, we demonstrated that GTF2E2 could be regulated by miR-340-5p directly or indirectly. CCND1 was transcriptionally affected by GTF2E2 and glioma progression was then regulated. Our data presented the overexpression of GTF2E2 in glioma and indicated the association between GTF2E2 and glioma prognosis. GTF2E2 was found to be regulated by miR-340-5p and thus affect downstream gene expressions and glioma progression. Our results indicate that GTF2E2 might be a potential target in the diagnosis and treatments of glioblastoma.

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Fig. 1: Unusual and heightened GTF2E2 expression detected in glioma, alongside the application of single-cell RNA-seq to investigated GTF2E2.
Fig. 2: in vitro experiment validated GTF2E2 function.
Fig. 3: In vivo experiment validated of the function of GTF2E2.
Fig. 4: GTF2E2 controlled the expression of CCND1 and influenced the cell cycle.
Fig. 5: MiR-340-5p impeded the advancement of glioma by targeting GTF2E2.
Fig. 6: Within the U87 cell line, miR-340-5p suppressed the expression of GTF2E2, resulting in the inhibition of proliferation and invasion, while fostering apoptosis.
Fig. 7: Metformin reinstated the expression of miR-340-5p, counteracted the impact of GTF2E2, and restrained U87 proliferation.
Fig. 8: In vivo verification of the tumor-suppressive impact of both miR-340-5p and metformin.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by the Natural Science Foundation of Anhui Province [grant number 2108085MH296], the Open Research Fund of Anhui Province Key Laboratory of High Field Magnetic Resonance Imaging [grant number KFKT-2020-0002], the Joint Fund for Medical Artificial Intelligence [grant number MAI2022Q011], and the Science and Technology Project grant from Anhui Province [grant number 202004j07020021].

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Author notes

  1. These authors contributed equally: Xiaolong Qiao, Yinan Chen, Zixuan Wang.

Authors and Affiliations

  1. Anhui University of Science and Technology, 232001, Huainan, Anhui, China

    Xiaolong Qiao & Chuandong Cheng

  2. Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, Anhui, China

    Xiaolong Qiao, Yinan Chen, Nan Peng, Wanxiang Niu, Ying Ji, Chaoshi Niu & Chuandong Cheng

  3. Dalian Medical University, 116000, Dalian, Liaoning, China

    Zixuan Wang

  4. Department of Neurosurgery, The Affiliated Chuzhou Hospital of Anhui Medical University, The First People’s Hospital of Chuzhou, 239000, Chuzhou, Anhui, China

    Shiqiang Hou

  5. Bengbu Medical College, 233000, Bengbu, Anhui, China

    Jiaying Wu

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Contributions

CC, YJ, and CN designed this project. XQ and ZW performed the experiments. NP, WN, and JW collected specimen. XQ and YC analyzed the data and wrote the paper. All authors have discussed the results and made comments on the experiment.

Corresponding authors

Correspondence to Ying Ji, Chaoshi Niu or Chuandong Cheng.

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All procedures involving human participants in this study were approved by the Research Ethics Committee of the First Affiliated Hospital of USTC. All patients included in the present study signed informed consent. All animal experiments were approved by the Animal Management Committee of the First Affiliated Hospital of USTC.

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Qiao, X., Chen, Y., Wang, Z. et al. GTF2E2 downregulated by miR-340-5p inhibits the malignant progression of glioblastoma. Cancer Gene Ther 30, 1702–1714 (2023). https://doi.org/10.1038/s41417-023-00676-1

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