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CDGSH Iron Sulfur Domain 2 Deficiency Inhibits Cell Proliferation and Induces Cell Differentiation of Neuroblastoma

Abstract

CDGSH iron sulfur domain 2 (CISD2) is reported to be highly expressed in several cancers, but the role of it in neuroblastoma has not been identified yet. Here, for the first time, we show that CISD2 is involved in neuroblastoma tumorigenesis and regulates neuroblastoma cell proliferation and differentiation. We found that high CISD2 expression correlated significantly with poor outcome of neuroblastoma patients, as well as advanced neuroblastoma tumor stages. Knockdown of CISD2 greatly repressed neuroblastoma cell proliferation and tumorigenesis both in vitro and in vivo. Further investigation showed that CISD2 deficiency resulted in cell cycle arrest in G1 phase and induced cell differentiation of neuroblastoma. Several Cyclins and Cyclin-Dependent Kinases (CDKs) were down-regulated by CISD2 knockdown, indicating that CISD2 probably regulates cell cycle through those genes. Together, we provide evidence that CISD2 is an indicator for neuroblastoma patients prognosis and is indispensable for neuroblastoma cell proliferation and tumorigenesis; CISD2 deficiency can induce neuroblastoma cell cycle arrest and differentiation. These findings suggest that CISD2 could work as a novel and potential therapeutic target for neuroblastoma treatment.

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Abbreviations

BrdU:

5-Bromo-2-deoxyuridine

CDK:

Cyclin-Dependent Kinase

CISD2:

CDGSH iron sulfur domain 2

DMEM:

Dulbecco’s modified Eagle’s medium

FBS:

fetal bovine serum

shRNA:

short hairpin RNA

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Acknowledgments

This work was supported by the National Key Research and Development Program of China (2017YFC1308600, 2016YFC1302204), the National Natural Science Foundation of China (No. 81672502), the Entrepreneurship and Innovation Program for Chongqing Overseas Returned Scholars (No. cx2017014), and the Chongqing University Innovation Team Building Program funded projects (CXTDX201601010).

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Correspondence to Mengying Huang.

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The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

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Li, J., Duan, H., Xuan, F. et al. CDGSH Iron Sulfur Domain 2 Deficiency Inhibits Cell Proliferation and Induces Cell Differentiation of Neuroblastoma. Pathol. Oncol. Res. 26, 1725–1733 (2020). https://doi.org/10.1007/s12253-019-00753-7

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Keywords

  • CDGSH iron sulfur domain 2
  • Neuroblastoma
  • Cell proliferation
  • Tumorigenesis
  • Differentiation