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Hsa_circ_0001361 facilitates cell progression and glycolytic metabolism in neuroblastoma via interacting with mir-490-5p to induce TRIM2 upregulation

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Abstract

Circular RNAs (circRNAs) can regulate the progression of neuroblastoma (NB) via miRNA/mRNA axis. This study aimed to investigate the functional mechanism of hsa_circ_0001361 in NB. Hsa_circ_0001361, miR-490-5p and tripartite motif 2 (TRIM2) were detected through reverse transcription-quantitative polymerase chain reaction. The proliferation ability was examined using cell counting kit-8 assay, colony formation assay and ethynyl-2’-deoxyuridine assay. Cell migration and invasion were assessed via transwell assay and wound healing assay. The protein levels were measured by western blot. Glycolysis was analyzed via commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed for target analysis. Hsa_circ_0001361 research in vivo was performed using xenograft tumor assay. Hsa_circ_0001361 was overexpressed in NB tissues and cells. Hsa_circ_0001361 downregulation suppressed cell proliferation, metastasis and glycolysis. Hsa_circ_0001361 served as a miR-490-5p sponge. The functions of hsa_circ_0001361 in NB cells were associated with miR-490-5p sponging effect. Hsa_circ_0001361 resulted in TRIM2 expression change via targeting miR-490-5p. MiR-490-5p acted as a tumor inhibitor in NB by downregulating TRIM2. Hsa_circ_0001361 knockdown reduced tumor growth in vivo through mediating miR-490-5p/TRIM2 axis. Our results suggested that hsa_circ_0001361 upregulated TRIM2 by absorbing miR-490-5p, thereby promoting cell malignant behaviors and glycolytic metabolism in NB.

Highlights

  1. 1.

    Silence of hsa_circ_0001361 inhibits cell proliferation, metastasis and glycolysis in NB.

  2. 2.

    Hsa_circ_0001361 targets miR-490-5p to increase TRIM2 expression.

  3. 3.

    Hsa_circ_0001361 enhanced tumor growth in vivo via miR-490-5p/TRIM2 axis.

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Data availability

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

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Contributions

Conceptualization and Methodology: Fang Lu and Shanshan Xu; Formal analysis and Data curation: Rongrong Lv and Shanshan Xu; Validation and Investigation: Rongrong Lv and Fang Lu; Writing - original draft preparation and Writing - review and editing: Rongrong Lv, Fang Lu and Shanshan Xu ; Approval of final manuscript: all authors.

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Correspondence to Shanshan Xu.

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The present study was approved by the ethical review committee of Laiyang Central Hospital of Yantai City. 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 that they have no competing interests.

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Fig. 9

Hsa_circ_0001361 enhanced tumor growth in vivo by regulating TRIM2. A-B Tumor volume and weight were measured in xenograft models of lenti-sh-NC, lenti-sh-hsa_circ_0001361, lenti-sh-hsa_circ_0001361 + vector and lenti-sh-hsa_circ_0001361 + TRIM2 groups. C The protein expression levels of ki-67, TRIM2, MMP2 and MMP9 were detected by IHC assay. *P < 0.05. (PNG 6.07 MB)

High Resolution Image (TIF 7.97 MB)

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Lv, R., Lu, F. & Xu, S. Hsa_circ_0001361 facilitates cell progression and glycolytic metabolism in neuroblastoma via interacting with mir-490-5p to induce TRIM2 upregulation. Metab Brain Dis 38, 1621–1632 (2023). https://doi.org/10.1007/s11011-023-01197-4

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