Abstract
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 of MIR155HG, as a long noncoding RNA, in TMZ resistance. In our study, MIR155HG level was markedly higher in glioma patients than in normal controls and that poor survival was positively correlated with MIR155HG expression. It was apparent that TMZ sensitivity was promoted by downregulation of MIR155HG, and this could be reversed by MIR155HG overexpression in vivo and in vitro. Furthermore, polypyrimidine tract binding protein 1 (PTBP1) was proven to bind with MIR155HG and to regulate MIR155HG-related TMZ resistance. Mechanistic investigation showed that the expression levels of both MIR155HG and PTBP1 influenced the expression of relevant proteins in the Wnt/β-catenin pathway. Collectively, the study demonstrated that the knockdown of MIR155HG increased glioma sensitivity to TMZ by inhibiting Wnt/β-catenin pathway activation via potently downregulating PTBP1.
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This work was financially supported by National Natural Science Foundation of China, Grant/Award Number: #81502161, Chongqing Science and Technology Commission, Grant/Award Numbers: #cstc2015jcyjA10007.
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In our research, XH finished the most part of experiments and wrote the manuscript. JS and WY helped finish some part of experiments. KW and SZ gave advice for experimental design, QL designed the experiments and modified the manuscript.
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S1
The stable overexpression of MIR155HG was measured. S2 The fluorescence level of PTBP1 in MIR155HG-altered cells was determined. S3 The fluorescence level of β-catenin influenced by MIR155HG was measured. S4 The fluorescence levels of PTBP1 and β-catenin after siPTBP1 transfection were determined. (The above scale bars = 100 μm) (XLSX 10 kb)
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He, X., Sheng, J., Yu, W. et al. LncRNA MIR155HG Promotes Temozolomide Resistance by Activating the Wnt/β-Catenin Pathway Via Binding to PTBP1 in Glioma. Cell Mol Neurobiol 41, 1271–1284 (2021). https://doi.org/10.1007/s10571-020-00898-z
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DOI: https://doi.org/10.1007/s10571-020-00898-z