Research On The Role Of Long Non-coding RNA BC200 In Regulating Myelodysplastic Syndrome Cells Proliferation And Its Mechanisms

Background: Myelodysplastic syndrome(MDS)is a group of heterogeneous clonal hematopoietic stem cell diseases,which is characterized by abnormal differentiation and development of blood cells,ineffective hematopoiesis and the risk of transformation to acute myeloid leukemia(AML).The occurrence and progression of MDS is a pathological process involving multi-gene and multi-step.The pathogenies of MDS are still unclear.Stem cell gene abnormality,cell cycle disorder,hematopoietic microenvironment changes,autoimmune deficiency may be involved in the pathogenesis of MDS.The malignant proliferation of MDS cells in bone marrow microenvironment is closely related to the occurrence and development of MDS.Long non-coding RNA(lncRNA)lacks specific and complete open reading frames(ORFs)and protein coding function.LncRNAs are >200 nucleotides in length.They play significant roles in regulating biological activities of cells,including proliferation,migration,invasion,differentiation and apoptosis.By investigating the specific role and molecular mechanism of lncRNA in MDS,a novel approach will be established to find the diagnostic and therapeutic targets for MDS.lncRNA BC200 is abnormally expressed and acts as an oncogene in a variety of cancers,but the mechanism and clinical significance of its abnormal expression in MDS are still unclear.Methods: The gene expression level of lncRNA BC200 in bone marrow mononuclear cells of MDS was analyzed through public database for bioinformatics analysis,and the expression of lncRNA BC200 in bone marrow mononuclear cells of clinical MDS patients was detected and identified by q RT-PCR.The effects of lncRNA BC200 in the proliferation,cell cycle and apoptosis of MDS cells was detected by CCK-8 assay,Ed U,colony formation assay and flow cytometry.A subcutaneous tumor model of NCG mice was constructed with sh-lncRNA BC200 MDS cells The interactions between lncRNA BC200 and transcription factor Myb were detected by chromatin immunoprecipitation(Ch IP)and luciferase reporter gene assay.Furthermore,the lncRNA-miRNA-m RNA ce RNA network was constructed to analyze the ce RNA network downstream of lncRNA BC200.The interactions between lncRNA BC200 and miR-150-5p were identified by RNA immunoprecipitation(RIP)and luciferase reporter gene assay.Results: The results showed that the expression of lncRNABC200 in bone marrow mononuclear cells of MDS patients was significantly higher than that of normal individuals.Knockdown of lncRNA BC200 inhibited MDS cell proliferation,colony formation and cell cycle progression in vitro,suppressed the growth of MDS cells in vivo and significantly inhibited the proliferation of primary cells of MDS patients.Mechanistic investigations revealed that lncRNA BC200 was a direct transcriptional target of transcription factor Myb and knockdown of transcription factor Myb abolished the oncogenic effect of lncRNA BC200.In addition,lncRNA BC200 is mainly located in the cytoplasm.The results further suggest that lncRNA BC200 functions as a miRNA sponge to regulate the expression of miR-150-5p.Conclusions: This results showed that the expression of protooncogene lncRNA BC200 was significantly increased in MDS;the transcription factor Myb was involved in the regulation of its transcriptional expression and promoted the malignant proliferation of MDS cells through the Myb/lncRNA BC200/miR-150-5p axis.