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LncRNA SNHG5 regulates SOX4 expression through competitive binding to miR-489-3p in acute myeloid leukemia

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Abstract

Objectives

Currently, lncRNA plays an important role in the occurrence and development of acute myeloid leukemia (AML), including SNHG5. However, the role and mechanism of SNHG5 in AML remains unclear. In this study, we explored the regulatory mechanism of SNHG5 in the development of AML.

Methods and results

QRT-PCR was used to investigate the expression of SNHG5, miR-489-3p, and SOX. The proliferation and apoptosis of AML cells were analyzed by cell transfection, cell counting kit-8 (CCK8), and flow cytometric analysis. Moreover, the expression analysis of marker proteins was detected by western blot. Through luciferase activity assay, RNA pull-down, and RNA-binding protein immunoprecipitation (RIP), we proved that SNHG5 could bind miR-489-3p and SOX4 which might be the target gene of miR-489-3p.

Results

We first found that SNHG5 was up-regulated in both AML patient bone marrow samples and various AML cell lines. Second, we found that knockdown of SNHG5 inhibited proliferation of AML cells and promoted apoptosis. It was found that SNHG5 could bind miR-489-3p, and the relative expression of SNHG5 was negatively correlated with miR-489-3p. Further results suggested that SOX4 might be the target gene of miR-489-3p. Finally, our experimental data indicated that knockdown of SNHG5 could reduce the tumor volume and down-regulated SOX4 levels in vivo.

Conclusions

Our results demonstrated that SNHG5 affected the expression of SOX4 through binding miR-489-3p to regulate proliferation and apoptosis of AML, which might act as a prospective prognostic biological marker and a promising therapeutic target for AML.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Authors and Affiliations

  1. Department of Clinical Hematology, Affiliated No. 2 Hospital School of Medicine, Xi’an Jiaotong University, Xi’an Jiaotong University West Five Road, No 157, Xi’an, 710004, People’s Republic of China

    Xiaoyang Ying & Wanggang Zhang

  2. Department of Hematology, Affiliated Zhongshan Hospital of Dalian University, Liaoning, Dalian, 116001, China

    Xiaoyang Ying, Meiyun Fang, Chenchen Wang, Li Han & Chenmeng Yang

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  1. Xiaoyang Ying
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Contributions

XYY and WGZ conceived and designed the experiments, MYF and CCW analyzed and interpreted the results of the experiments, and LH and CMY performed the experiments.

Corresponding author

Correspondence to Wanggang Zhang.

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The authors declare that they have no competing interests, and all authors should confirm its accuracy.

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The animal use protocol listed below has been reviewed and approved by the Animal Ethical and Welfare Committee.

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11_2020_1345_MOESM1_ESM.jpg

Figure S1 The cell cycle examined by flow cytometry about the effects of SNHG5 knockdown on cells cycle in KG-1a and HL-60 cells. Figure S2 Cells cycle detected by flow cytometry in KG-1a and HL-60 cells transfected with inh NC and si-NC, inh NC and si-SNHG5, or si-SNHG5 and miR-489-3p inh (JPG 3063 kb)

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Ying, X., Zhang, W., Fang, M. et al. LncRNA SNHG5 regulates SOX4 expression through competitive binding to miR-489-3p in acute myeloid leukemia. Inflamm. Res. 69, 607–618 (2020). https://doi.org/10.1007/s00011-020-01345-x

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  • DOI: https://doi.org/10.1007/s00011-020-01345-x

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