The Mechanism Of Hsa-CircRNA-0001009 Targeting And Regulating MiRNA-22-3P/HMGB1 Pathway In Medulloblastoma Biological Function

Object:To explore the effect of circular RNA（Circular RNA,CircRNA）hsaCircRNA-0001009 on the biological function of medulloblastoma by targeting the regulation of miRNA-22-3P/HMGB1 pathway.Methods: The upstream target gene hsa-CircRNA-0001009 of miRNA-22-3P was screened by microarray.Double luciferase further verified the molecular sponge relationship between miRNA-22-3P and hsa-CircRNA-0001009.Consult the relevant literature to predict the downstream target gene HMGB1 of miRNA-22-3P.The expression of hsa-circ RNA-0001009 in clinical specimens of medulloblastoma was verified by qRT-PCR,and the expression and localization of HMGB1 protein were detected by WB and immunohistochemistry.The medulloblastoma cell line DAOY with low expression of hsa-circ RNA-0001009 was constructed by lentivirus,and the effect of inhibiting the expression of hsa-circ RNA-0001009 on the expression of miRNA-22-3P and HMGB1 was verified.Then,the effect of hsa-CircRNA-0001009 on the biological function of medulloblastoma DAOY cells was explored by CCK-8experiment,cell clone formation,cell wound healing,Transwell chamber invasion and migration,and flow cytometry.The effect of miRNA-22-3P inhibition on the expression of hsa-CircRNA-0001009 and HMGB1 protein was explored using miRNA-22-3P inhibitor.The effects on proliferation,apoptosis and expression of cells were verified again.Finally,an animal xenograft model was used to observe the effect of hsaCircRNA-0001009 expression on in vivo tumors.Results: The expression of Hsa-CircRNA-0001009 and HMGB1 was elevated in medulloblastoma tissue compared with normal brain tissue.Hsa-CircRAN-0001009,acting as a molecular sponge of miR-22-3P,regulated the proliferation,migration,invasion and apoptosis of medulloblastoma DAOY cell line,and further regulated the expression of the downstream target gene HMGB1.The mouse xenograft model also confirmed that the low expression of Hsa-CircRNA-0001009 inhibited the proliferation of tumors.At the same time,inhibiting the expression of miR-22-3P promoted the expression of Hsa-CircRNA-0001009 and HMGB1,and promoted the proliferation of tumors and inhibited tumor apoptosis.Conclusions: Hsa-CircRNA-0001009 and miRNA-22-3P/HMGB1 constitute a regulatory pathway for medulloblastoma,which affects the proliferation,migration,invasion and apoptosis of medulloblastoma DAOY cell line,and may become a therapeutic target for medulloblastoma.