Long Noncoding RNA SOCS2-AS Promotes Leukemogenesis in FLT3-ITD+ Acute Myeloid Leukemia Through miRNA-221

LncRNAs play an important role in tumorigenesis and development in tumors, but the function of lncRNA SOCS2-AS in acute myeloid leukemia (AML) is unknown.

In the present study, we used RT-PCR to detect the expression of SOCS2-AS in FLT3-ITD+, FLT3-ITD- AML patients and different AML cell lines. The colony formation and CCK-8 assay were performed to analyze the proliferation ability, and the flow cytometry was performed to analyze the capacity of apoptosis in Molm-13 and MV4-11 cells. The Western blot was applied to detect the expression of STAT5 and p-STAT5. The RNA pull-down and luciferase activity were used to investigate the interaction between SOCS2-AS and miR-221.

The results indicate that SOCS2-AS shows overexpression in FLT3-ITD+ AML patients compared to FLT3-ITD- AML patients. Si-SOCS2-AS can inhibit the proliferation, boost the apoptosis and induce the cycle arrest in Molm-13 cells, and SOCS2-AS overexpression promotes proliferation and colony formation in MV4-11 cells. The miR-221 shows overexpression in FLT3-ITD+ AML patients compared to FLT3-ITD- AML patients. And the expression level of miR-221 and SOCS2-AS shows negative correlation in FLT3-ITD+ AML patients. Functionally, SOCS2-AS could be interacted with miR-221 in AML cells. After SOCS2-AS knockdown, the phosphorylation level of STAT5 was significantly decreased. Moreover, miR-221 inhibitor can rescue the viability in cells after si-SOCS2-AS transfection. And it is stated that SOCS2-AS regulates the STAT5 signal transduction pathway with sponging miR-221.

In conclusion, this study confirms the molecular mechanism of SOCS2-AS in AML by targeting the miR-221/STAT5 signaling pathway. This indicates SOCS2-AS may serve as a potential therapeutic target for the treatment of AML.