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

Abstract

Background: 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. Materials and Methods: 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 pulldown and luciferase activity were used to investigate the interaction between SOCS2-AS and miR-221. Results: 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. Conclusion: 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.

The RNA editing landscape in acute myeloid leukemia reveals associations with disease mutations and clinical outcome

“…It has recently been reported that SOCS2-AS1 modulates FLT3-ITD activity via sponging miRNA-221 activity to maintain STAT5 signal transduction. 23 However, we observed no significant differences in FLT3 mutational status between the number of patients with (11/32 cases, 34%) and those that lacked an RDD (33/119, 28%). Moreover, the AEI also did not alter between patients that carried or lacked the FLT3-ITD mutation ( Figure 5 C).…”

LncSIK1 enhanced the sensitivity of AML cells to retinoic acid by the E2F1/autophagy pathway

“…It is worth discussing the regulatory axis of lncRNA/E2F1 in this contradictory network. Supporting evidence has shown that several lncRNAs are related to FLT3‐ITD, including LncH19, 37 LncSOCS2‐AS, 38 LncTUG1 39 and LncCCAT2 40 . Among them, LncH19, LncTUG1 and LncCCAT2 were implicated in autophagy and E2F1.…”

miR-221/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: A systematic review

“…Zhang et al mechanically demonstrated that SOCS2-AS acts as a proto-oncogene and promotes FLT3-ITD+ AML progression by regulation of STAT5 pathway through miR-221 sponging. 107 Deng et al analyzed two datasets of miR profiling in AML patients, discovering that miR-221 was upregulated in both models. To further understand the biological function of miR-221 in AML leukemogenesis, they evaluated, both in silico and in vitro, the potential role of miR-221 in epigenetic pathway regulation, and demonstrated the existence of NCL/miR-221/NF-kB/DNMT1 epigenetic regulatory network that modulates p27kip1 and p15INK4B.…”