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Circular RNA VPS18 Promotes Glioblastoma Progression by Regulating miR-1229-3p/BCAT1 Axis

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Abstract

Circular RNAs (circRNAs) have been verified to play important roles in malignant tumors, including glioblastoma. The aim of this study is to explore the biological roles and underlying mechanisms of circRNA vacuolar protein sorting 18 homolog (circVPS18) in glioblastoma. A quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the expression of circVPS18, microRNA (miR)-1299-3p, and branched-chain amino acid transaminase 1 (BCAT1). In vitro experiments were conducted using 5-ethynyl-2′-deoxyuridine (EdU), flow cytometry, transwell, and tube formation assays, respectively. Western blot was conducted to examine all protein levels. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to confirm the interaction between miR-1229-3p and circVPS18 or BCAT1. The murine xenograft model was established to conduct in vivo assay. CircVPS18 and BCAT1 were highly expressed while miR-1229-3p was lowly expressed in glioblastoma tissues and cells. CircVPS18 knockdown inhibited glioblastoma progression by inhibiting cell proliferation, migration, invasion, and angiogenesis, and promoting cell apoptosis. Moreover, miR-1229-3p could be targeted by circVPS18; inhibition of miR-1229-3p could invert the suppressive effect of circVPS18 knockdown on glioblastoma tumorigenesis. Furthermore, BCAT1 was a target of miR-1229-3p; functionally, BCAT1 overexpression could reverse the inhibitory effects of miR-1229-3p upregulation on glioblastoma cell malignant phenotypes. Moreover, we also verified that circVPS18A could regulate BCAT1 expression by sponging miR-1229-3p. Additionally, circVPS18 silencing also restrained tumor growth and metastasis in vivo. CircVPS18 accelerated glioblastoma progression by miR-1229-3p/BCAT1 axis, providing a potential therapeutic target for glioblastoma.

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Availability of Data and Materials

The analyzed data sets generated during the present study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Neurosurgery, Ganzhou People’s Hospital of Jiangxi Province, No. 16 Meiguan Avenue, Zhanggong District, Ganzhou, 341000 Jiangxi Province, China

    Qianliang Huang, Wei Li, Yu Huang, Qiang Chen & Wenjin Wei

Authors
  1. Qianliang Huang
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  2. Wei Li
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  3. Yu Huang
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  4. Qiang Chen
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  5. Wenjin Wei
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Contributions

Conceptualization and methodology: Wei Li and Yu Huang; formal analysis and data curation: Yu Huang, Qiang Chen, and Wenjin Wei; validation and investigation: Qianliang Huang, Wei Li, and Qiang Chen; writing–original draft preparation and writing–review and editing: Qianliang Huang, Wei Li, and Yu Huang; approval of the final manuscript: all authors.

Corresponding author

Correspondence to Wei Li.

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Ethics Approval and Consent to Participate

The present study was approved by the ethical review committee of Ganzhou People's Hospital of Jiangxi Province. Written informed consent was obtained from all enrolled patients.

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Patients agree to participate in this work.

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The authors declare no competing interests.

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Highlights

• CircVPS18 was highly expressed in glioblastoma tissues and cells.

• CircVPS18 downregulation suppressed the progression of glioblastoma by regulating miR-1229-3p activity.

• MiR-1229-3p exerted the anti-tumor role in glioblastoma cells by downregulating BCAT1.

• CircVPS18 acted as a miR-1229-3p sponge to regulate BCAT1 expression.

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Huang, Q., Li, W., Huang, Y. et al. Circular RNA VPS18 Promotes Glioblastoma Progression by Regulating miR-1229-3p/BCAT1 Axis. Neurotox Res 40, 1138–1151 (2022). https://doi.org/10.1007/s12640-022-00530-6

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  • DOI: https://doi.org/10.1007/s12640-022-00530-6

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