CDGSH Iron Sulfur Domain 2 Deficiency Inhibits Cell Proliferation and Induces Cell Differentiation of Neuroblastoma
- 45 Downloads
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.
KeywordsCDGSH iron sulfur domain 2 Neuroblastoma Cell proliferation Tumorigenesis Differentiation
CDGSH iron sulfur domain 2
Dulbecco’s modified Eagle’s medium
fetal bovine serum
short hairpin RNA
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).
Compliance with Ethical Standards
Conflict of Interest
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.
- 15.Sohn YS, Tamir S, Song L, Michaeli D, Matouk I, Conlan AR, Harir Y, Holt SH, Shulaev V, Paddock ML, Hochberg A, Cabanchick IZ, Onuchic JN, Jennings PA, Nechushtai R, Mittler R (2013) NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth. Proc Natl Acad Sci U S A 110(36):14676–14681CrossRefGoogle Scholar
- 21.Chang L, Goldman RD (2004) Intermediate filaments mediate cytoskeletal crosstalk. Nature reviews. Mol Cell Biol 5(8):601–613Google Scholar
- 24.Tamir S, Zuris JA, Agranat L, Lipper CH, Conlan AR, Michaeli D, Harir Y, Paddock ML, Mittler R, Cabantchik ZI, Jennings PA, Nechushtai R (2013) Nutrient-deprivation autophagy factor-1 (NAF-1): biochemical properties of a novel cellular target for anti-diabetic drugs. PLoS One 8(5):e61202CrossRefGoogle Scholar
- 31.Yang L, Huang M, Tan J, Hou J, He J, Wang F, Cui H, Yi L (2017) Transcriptional co-activator with PDZ-binding motif overexpression promotes cell proliferation and transcriptional co-activator with PDZ-binding motif deficiency induces cell cycle arrest in neuroblastoma. Oncol Lett 13(6):4295–4301CrossRefGoogle Scholar