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Circular RNA circRNA_0000094 sponges microRNA-223-3p and up-regulate F-box and WD repeat domain containing 7 to restrain T cell acute lymphoblastic leukemia progression

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A Correction to this article was published on 06 July 2021

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Abstract

Circular RNAs (circRNAs) exert crucial regulatory effects in the pathogenesis of multiple tumors. This work aimed to probe into the role of circ_0000094 in T cell acute lymphoblastic leukemia (T-ALL). In this work, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to quantify circ_0000094, miR-223-3p, and F-box and WD repeat domain containing 7 (FBW7) mRNA expressions in lymph node samples from T-ALL patients; Western blot was adopted to examine FBW7 protein expression in T-ALL cells; cell proliferation was detected by cell counting kit-8 (CCK-8) experiment; apoptosis was examined by flow cytometry; Transwell experiments were applied to assess T-ALL cell migration and invasion; the interactions among circ_0000094 and miR-223-3p, and miR-223-3p and FBW7 were validated by bioinformatics prediction, dual-luciferase reporter gene assay, and RNA immunoprecipitation experiment. We reported that, circ_0000094 expression was markedly reduced in T-ALL and circ_0000094 was predominantly located in the cytoplasm; gain-of-function and loss-of-function assays verified that circ_0000094 overexpression remarkably suppressed T-ALL cell proliferation, migration, and invasion, and enhanced apoptosis while knocking down circ_0000094 enhanced the malignant phenotypes of T-ALL cells; “rescue experiments” implied that miR-223-3p mimics partly reversed the inhibitory effects on the malignant phenotype of T-ALL cells due to the circ_0000094 up-regulation; circ_0000094 was proved to be a molecular sponge for miR-223-3p, and it could up-regulate the expression of FBW7 via repressing miR-223-3p expression. Taken together, it was concluded that circ_0000094 impedes T-ALL progression by modulating the miR-223-3p/FBW7 axis.

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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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Acknowledgements

We thank Hubei Yican Health Industry Co., Ltd. (Wuhan, China) for its linguistic assistance during the preparation of this manuscript.

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  1. Yan Hou, Junjie Sun, Jie Huang, Fengzhi Yao and Xuelian Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, Hubei, China

    Yan Hou & Dongchi Zhao

  2. Department of Pediatrics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136 Jingzhou Street, Xiangcheng District, Xiangyang City, 441021, Hubei Province, China

    Yan Hou, Junjie Sun, Jie Huang, Fengzhi Yao, Xuelian Chen & Bin Zhu

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  1. Yan Hou
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Correspondence to Bin Zhu or Dongchi Zhao.

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This study was approved by the Ethics Committee of Xiangyang Central Hospital (Approval number: XYCH201801C03).

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13577_2021_504_MOESM1_ESM.tif

Supplementary file1 (TIF 116 KB) Figure 1 (A-B) The T-ALL cells were treated with various concentrations of gamma-secretase inhibitors (GSIs) for 48 h. Then the viability of T-ALL cells was detected by CCK-8 assay. CCK-8, cell counting kit-8. All experiments were performed in triplicate. *** P < 0.001

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Hou, Y., Sun, J., Huang, J. et al. Circular RNA circRNA_0000094 sponges microRNA-223-3p and up-regulate F-box and WD repeat domain containing 7 to restrain T cell acute lymphoblastic leukemia progression. Human Cell 34, 977–989 (2021). https://doi.org/10.1007/s13577-021-00504-4

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