LncRNA LINC00265/miR-4855p/IRF2-mediated Autophagy Suppresses Apoptosis In Acute Myeloid Leukemia Cells

Background : Acute myeloid leukemia(AML)is a heterogeneous hematologic malignancies characterized by clonal expansion of myeloid cells in peripheral blood,bone marrow(BM),and/or other tissues.In recent years,despite the rapid progress of chemotherapy and molecular targeted therapy,AML has many molecular changes,its mechanism remains unclear,and the prognosis and long-term survival rate of patients are still low.The pathogenesis of AML involves a variety of genes,and further elucidation of the molecular mechanism of its pathogenesis may provide new targeted therapies for AML.Objective:In recent years,a number of studies have shown that long non-coding RNAs(lnc RNAs)are involved in the occurrence and development of tumors,such as lung non-small cell carcinoma,ovarian tumor,bladder cancer,liver tumor,etc.,and regulate the growth of tumor cells through certain specific channels in different cancers.Lnc RNAs are usually more than 200 nucleotides in length,do not contain open reading frames and do not participate in protein synthesis.LINC00265 is a novel long-chain non-coding RNA.Studies have shown that it may regulate the proliferation,migration and invasion functions of AML cells through the regulation of PI3K/ Akt signaling pathway.However,the regulation of LINC00265 on autophagy and apoptosis of AML cells has not been clarified.A large number of studies have shown that long non-coding RNAs(lnc RNAs)play an important role in a variety of cancers.Methods : The effect of LINC00265 on AML was investigated by function gain or function loss experiment in AML cells.Beclin-1,p62 levels and LC3-II/LC3-I ratio were detected to detect autophagy.The proliferation and apoptosis of AML cells were detected by CCK-8 and flow cytometry,respectively.The interaction between miR-485-5p and LINC00265 was enhanced by RNA pull-down.The interaction between miR-485-5p and IRF2 3’UTR was analyzed by luciferase reporter gene assay.Results:The expression of LINC00265 was significantly up-regulated in the serum and AML cell lines of AML patients,while the expression of miR-485-5p was down-regulated.LINC00265 promoted autophagy in AML cells,while miR-485-5p inhibited autophagy.Conclusion:The expression of LINC00265 was significantly up-regulated in the serum and AML cell lines of AML patients,while the expression of miR-485-5p was down-regulated.LINC00265 promoted autophagy in AML cells,while miR-485-5p inhibited autophagy.Mechanically speaking,LINC00265 promotes the expression of IRF2 as a ce RNA of miR-485-5p.More importantly,LINC00265 overexpression or miR-485-5p inhibitors reversed the proliferation inhibition and pro-apoptotic effects mediated by 3-methyladenine(3-MA,an autophagy inhibitor),while silence of LINC00265 or miR-485-5p mimics reversed the proliferation-promoting and anti-apoptotic effects of the autophagy activator rapamycin.