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Circular RNA circKIF2A Contributes to the Progression of Neuroblastoma Through Regulating PRPS1 Expression by Sponging miR-377-3p

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Abstract

Neuroblastoma is a malignant tumor originating from the primitive neural crest. Circular RNA (circRNA) Kinesin Superfamily Protein 2A (circKIF2A, also known as hsa_circ_0129276) has been reported to be upregulated in neuroblastoma. However, the molecular mechanism of circKIF2A participated in neuroblastoma is poorly defined. We analyzed the expression levels of circKIF2A, microRNA-377-3p (miR-377-3p), and phosphoribosyl pyrophosphate synthetase 1 (PRPS1) in neuroblastoma tissues and cell lines (SK-N-AS and LAN-6) and explored their roles. The expression levels of CircKIF2A and PRPS1 were increased and that of miR-377-3p were decreased in 21 neuroblastoma tissues and cells. Functionally, the silencing of circKIF2A inhibited cell proliferation, migration, invasion, and glycolysis, boosted apoptosis in neuroblastoma cells in vitro, and blocked the growth of subcutaneously transplanted tumors in nude mice. Mechanically, circKIF2A could work as a sponge of miR-377-3p to enhance PRPS1 expression. CircKIF2A knockdown impedes cell proliferation, metastasis, and glycolysis partly by regulating the miR-377-3p/PRPS1 axis, suggesting that targeting circKIF2A can be a feasible therapeutic strategy for neuroblastoma.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

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  1. Department of Pediatrics, Xiantao first people’s Hospital Affiliated to Changjiang University, Shazui Street, Xiantao, 433000, Hubei, China

    Quan Jin, Jianmu Li, Fan Yang, Lingling Feng & Xin Du

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  1. Quan Jin
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Supplementary file1 (DOC 32 kb)

10528_2021_10174_MOESM2_ESM.tif

Supplementary Figure S1. CircKIF2A deficiency could hinder proliferation, migration, invasion, glycolysis, and accelerate apoptosis of IMR-32 cells. IMR-32 cells were transfected with si-NC and si-circKIF2A. (A) CircKIF2A level was assessed in transfected IMR-32 cells by RT-qPCR assay. (B-D) Cell proliferation was analyzed by MTT assay, EdU assay, and Colony formation assay in transfected IMR-32 cells. (E) Apoptosis rate was detected Flow cytometry assay in transfected IMR-32 cells. (F) PCNA, Bcl-2, and Bax protein levels were determined by Western blot assay in transfected IMR-32 cells. (G and H) The abilities of migration and invasion were measured by Transwell assays in transfected IMR-32 cells. (I and J) Levels of glucose consumption and lactate production were evaluated by the corresponding kits in transfected IMR-32 cells. (K) HK2 and LDHA protein levels were tested by Western blot assay in transfected IMR-32 cells. *P <0.05. (TIF 4573 kb)

10528_2021_10174_MOESM3_ESM.tif

Supplementary Figure S2. The effects of miR-377-3p on 5 potential target mRNAs in neuroblastoma cells. (A and B) Western blot analysis of ABI1, PHF20, PRPS1, ROBO2, and STAT2 protein levels in SK-N-AS and LAN-6 cells transfected with miR-377-3p mimic or miR-NC. *P <0.05, **P <0.01, ***P <0.001. (TIF 301 kb)

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Jin, Q., Li, J., Yang, F. et al. Circular RNA circKIF2A Contributes to the Progression of Neuroblastoma Through Regulating PRPS1 Expression by Sponging miR-377-3p. Biochem Genet 60, 1380–1401 (2022). https://doi.org/10.1007/s10528-021-10174-4

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