LncRNA MIR155HG Promotes Temozolomide Resistance by Activating the Wnt/β-Catenin Pathway Via Binding to PTBP1 in Glioma

被引:35
作者
He, Xin [1 ]
Sheng, Jie [1 ]
Yu, Wei [1 ]
Wang, Kejian [1 ]
Zhu, Shujuan [1 ]
Liu, Qian [1 ]
机构
[1] Chongqing Med Univ, Inst Neurosci, Chongqing, Peoples R China
基金
中国国家自然科学基金;
关键词
MIR155HG; Glioma; Drug resistance; PTBP1; Wnt; beta-catenin; LONG NONCODING RNA; CELL-LINES; MESENCHYMAL TRANSITION; SIGNALING PATHWAY; TUMOR-SUPPRESSOR; GLIOBLASTOMA; CHEMORESISTANCE; CONTRIBUTES; MODULATION; APOPTOSIS;
D O I
10.1007/s10571-020-00898-z
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Temozolomide (TMZ) is widely used for glioma therapy in the clinic. Currently, the development of TMZ resistance has largely led to poor prognosis. However, very little is understood about the role ofMIR155HG, as a long noncoding RNA, in TMZ resistance. In our study,MIR155HGlevel was markedly higher in glioma patients than in normal controls and that poor survival was positively correlated withMIR155HGexpression. It was apparent that TMZ sensitivity was promoted by downregulation ofMIR155HG, and this could be reversed byMIR155HGoverexpression in vivoandin vitro. Furthermore, polypyrimidine tract binding protein 1 (PTBP1) was proven to bind withMIR155HGand to regulateMIR155HG-related TMZ resistance. Mechanistic investigation showed that the expression levels of bothMIR155HGandPTBP1influenced the expression of relevant proteins in theWnt/beta-cateninpathway. Collectively, the study demonstrated that the knockdown ofMIR155HGincreased glioma sensitivity to TMZ by inhibitingWnt/beta-cateninpathway activation via potently downregulating PTBP1.
引用
收藏
页码:1271 / 1284
页数:14
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