[Expression of Ribonucleotide Reductase M2 in Patients with Multiple Myeloma and Its Mechanism Inhibiting Tumor Cell Proliferation].

OBJECTIVE

To investigate the expression of ribonucleotide reductase M2 (RRM2) in patients with multiple myeloma and its mechanism of inhibiting human multiple myeloma cell proliferation.

METHODS

Thirty-Six patients with multiple myeloma in our hospital from July 2016 to September 2018 were selected as MM group, at the same time simple iron deficiency anemia patients were taken as the control group. RT-qPCR and Western blot techniques were used to determine the mRNA and protein expression of RRM2 in bone marrow mononuclear cells, respectively. siRNAs oligos targeting RRM2 was transfected into RPMI8226 cells to establish the RRM2 silence model. CCK-8 and flow cytometry were used to analyze the cell proliferation and the cell cycle, and Western blot was used to detect the expression of cell cycle related proteins.

RESULTS

The expression level of RRM2 mRNA and the expression level of RRM2 protein in multiple myeloma group were significantly higher than those in control group (P＜0.05). Further analysis indicated that the level of RRM2 expression closely correlated with ISS staging, bone destruction and extramedullary infiltration (P＜0.05). Transfection with siRNAs targeting RRM2 could significantly down regulate the RRM2 expression. And the RRM2 down regulation inhibited the cell proliferation and arrested the cell cycle at S stage (P＜0.05). Further study indicated that RRM2 silencing influenced cell cycle-related proteins expression.

CONCLUSION

RRM2 overexpressies in bone marrow mononuclear cells of MM patients, moreover significantly relates with the degree of malignancy. The silencing RRM2 in multiple myeloma cells can inhibit cell proliferation through arresting cell cycle at S phase. RRM2 may be a marker to predict the prognosis of patients with multiple myeloma and novel target for new drug development.