Y-box protein-1 modulates circSPECC1 to promote glioma tumorigenesis via miR-615-5p/HIP1/AKT axis  

作　　者：Ping Lan Meihe Li Ying Wang Jingwen Wang Luyao Li Sha Zhang Xuan Zhang Caihong Ran Jin Zheng Huilin Gong 

机构地区：[1]Department of Nephrology,Hospital of Nephrology,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China [2]Department of Renal Transplantation,Hospital of Nephrology,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China [3]Department of Pathology,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China [4]Department of Pathology,Ngari Prefecture People’s Hospital,Ngari Prefecture 859099,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第12期1902-1912,共11页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Shaanxi Basic Research Program of Natural Science (No.2021JQ-392);the International Cooperation Program of Shaanxi Province (No.2021KW-47).

摘　　要：Y-box binding protein-1(YB-1)is upregulated in glioma and plays an important role in its occurrence and drug resistance.However,the involved regulatory processes and downstream pathways are still unclear.Since various circular RNAs(circRNAs)and microRNAs(miRNAs)also play roles in the pathogenesis of glioma,we hypothesize that YB-1 may exert its function through a circRNA-miRNA-protein interaction network.In this study,we use the RNA binding protein immunoprecipitation assay and quantitative reverse transcription polymerase chain reaction to determine the circRNAs involved in the regulation of YB-1 and further elucidate their biological functions.The level of circSPECC1(hsa_circ_0000745)modulated by YB-1 is significantly upregulated in the U251 and U87 glioma cell lines.Downregulation of circSPECC1 markedly inhibits the proliferation and invasiveness of U251 and U87 cells by inducing apoptosis.Bioinformatics analysis reveals that miR-615-5p could interact with circSPECC1 and huntingtin-interacting protein-1(HIP-1).Then we determine the interactions between miR-615-5p,circSPECC1,and HIP1 using dual luciferase reporter system and pull-down assays.Mechanistic analysis indicates that the downregulation of circSPECC1 results in a decreased HIP1 expression.This study demonstrates that circSPECC1 modulated by YB-1 is increased in glioma cell lines.In addition,circSPECC1 promotes glioma growth through the upregulation of HIP1 by sponging miR-615-5p and targeting the HIP1/AKT pathway.This indicates that YB-1 and circSPECC1 may both be promising targets for glioma treatment.

关 键 词：GLIOMA YB-1 circSPECC1 miR-615-5p HIP1 

分 类 号：R739.41[医药卫生—肿瘤]