The Expression And Significance Of SUMOylation In Insulin-like Growth Factor Ⅰ Receptor In Acute Myeloid Leukemia

Background and aim of the study:In recent years, due to the characteristics of insulin-like growth factorⅠreceptor (IGF-Ⅰreceptor) in tumor cell proliferation, apoptosis and transfer, it gradually becomes research hotspot in cancer targeted therapy. As a kind of across-membrane proteins, IGF-Ⅰreceptor has been found in the nucleus on the basis of its modification called SUMOylation. It is speculated that this modification plays some role in tumor. To explore the significance of targeted therapy by inhibiting IGF-Ⅰreceptor in acute myeloid leukemia (AML), this study observed SUMOylation in IGF-Ⅰreceptor and its influence in proliferation and apoptosis of the acute primitive myeloid leukemia cell lines (FIL-60).Methods:(1) Seven cases of acute myeloid leukemia and ten healthy subjects were recruited. (2) HL-60 lines were cultured. (3)The expression of IGF-Ⅰreceptor on cell surface was detected by Flow Cytometry (FCM). (4) The co-expressions of IGF-Ⅰreceptor and SUMO (small ubiquitin-related modifier) protein were determined by Immunofluorescence. (5) After suppressing the SUMO-conjugating enzyme UBC9 by UBC9 antibody, cell proliferation was tested by CCK-8, cell apoptosis was observed by dual dyeing of Annexin V-FITC&PI, and the co-expression of IGF-Ⅰreceptor and SUMO protein were determined by Immunofluorescence.Results:(1) Compared with normal control group, the expression level of IGF-Ⅰreceptor on the cell surface of HL-60 lines was higher (P<0.05). (2) There were some co-expressions of IGF-Ⅰreceptor and SUMO protein in abundance in the nucleus of the HL-60 lines and the AML cells, their positive cells were (74.17±2.90)% and (64.79±12.14)%.On the contrary, there was few or no co-expression in the cells of normal control group.(3)After 24 hours,48hours and 72hours of suppressing the expression of UBC9 by UBC9 antibody, the prolifer-ation of HL-60 cells was decreased, and there was obvious dose-response relationship(P<0.05) and time-effect relationship(P<0.05), the inhibition on apoptosis of HL-60 cells was not very significant, especially the dose-response relationship(P>0.05),while the time-effect relationship was there (P<0.05).And the co-expressions of IGF-Ⅰreceptor and SUMO in the nucleus of HL-60 cells was reduced significantly(39.29±8.52)%after 48hours of intervention.Conclusion:The expressions of IGF-Ⅰreceptor in AML cell surface were upregulated, and the SUMOylation IGF-Ⅰreceptor can be observed. After inhibiting UBC9, co-expressions of IGF-Ⅰreceptor and SUMO protein were significantly reduced, and cell proliferation was also suppressed. It pointed that SUMOylation mediated IGF-Ⅰreceptor entering the cell nucleus, and positively correlated with cell proliferation.