IGF-IR promotes clonal cell proliferation in myelodysplastic syndromes via inhibition of the MAPK pathway
| Autor: | Qingqing Zheng, Xiao Li, Chunkang Chang, Wen-Hui Shi, Feng Xu, Sida Zhao, Qi He, Juan Guo, Zheng Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Adult Male Cancer Research Adolescent MAP Kinase Signaling System IGF-IR proliferation Cell Apoptosis clonal cell Receptor IGF Type 1 03 medical and health sciences 0302 clinical medicine Growth factor receptor hemic and lymphatic diseases Cell Line Tumor medicine Humans Aged Cell Proliferation Podophyllotoxin Gene knockdown Chemistry Cell growth Cell Cycle Computational Biology General Medicine Articles Cell cycle Middle Aged MAPK myelodysplastic syndrome 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Gene Knockdown Techniques Myelodysplastic Syndromes Cancer research Picropodophyllin Female K562 Cells Transcriptome |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 1021-335X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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