Open Access

IGF‑IR promotes clonal cell proliferation in myelodysplastic syndromes via inhibition of the MAPK pathway

  • Authors:
    • Qi He
    • Qingqing Zheng
    • Feng Xu
    • Wenhui Shi
    • Juan Guo
    • Zheng Zhang
    • Sida Zhao
    • Xiao Li
    • Chunkang Chang
  • View Affiliations

  • Published online on: June 19, 2020     https://doi.org/10.3892/or.2020.7652
  • Pages: 1094-1104
  • Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Type 1 insulin‑like growth factor receptor (IGF‑IR) signaling is considered to serve a key role in the development of cancer. However, the effects of IGF‑IR on the malignant characteristics of myelodysplastic syndrome (MDS) clonal cells remains to be determined. In the present study it was demonstrated that knockdown of IGF‑IR reduced the proliferation and increased the apoptosis of MDS/leukemia cells. Integrated analysis of gene expression profiles using bioinformatics identified the MAPK signaling pathway as a critical downstream factor of IGF‑IR, and this was confirmed in vitro using western blotting which revealed that IGF‑IR knockdown significantly increased the expression of activated MAPK. Furthermore, IGF‑IR signaling was inhibited to investigate the potential of IGF‑IR as a therapeutic target of MDS. The results revealed that the IGF‑IR inhibitor picropodophyllin (PPP) inhibited cell proliferation, promoted cell apoptosis and arrested the cell cycle at the G2/M phase in MDS/leukemia cells. Similar to the effects of IGF‑IR knockdown, PPP treatment also increased MAPK signaling in vitro. In conclusion, IGF‑IR may serve as a potential therapeutic target of MDS.
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September-2020
Volume 44 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
He Q, Zheng Q, Xu F, Shi W, Guo J, Zhang Z, Zhao S, Li X and Chang C: IGF‑IR promotes clonal cell proliferation in myelodysplastic syndromes via inhibition of the MAPK pathway. Oncol Rep 44: 1094-1104, 2020
APA
He, Q., Zheng, Q., Xu, F., Shi, W., Guo, J., Zhang, Z. ... Chang, C. (2020). IGF‑IR promotes clonal cell proliferation in myelodysplastic syndromes via inhibition of the MAPK pathway. Oncology Reports, 44, 1094-1104. https://doi.org/10.3892/or.2020.7652
MLA
He, Q., Zheng, Q., Xu, F., Shi, W., Guo, J., Zhang, Z., Zhao, S., Li, X., Chang, C."IGF‑IR promotes clonal cell proliferation in myelodysplastic syndromes via inhibition of the MAPK pathway". Oncology Reports 44.3 (2020): 1094-1104.
Chicago
He, Q., Zheng, Q., Xu, F., Shi, W., Guo, J., Zhang, Z., Zhao, S., Li, X., Chang, C."IGF‑IR promotes clonal cell proliferation in myelodysplastic syndromes via inhibition of the MAPK pathway". Oncology Reports 44, no. 3 (2020): 1094-1104. https://doi.org/10.3892/or.2020.7652