Knockdown of long noncoding RNA H19 sensitizes human glioma cells to temozolomide therapy

作者: Weiguo Li , Xiangyu Ma , Rucai Zhan , Pengfei Jiang , Ping Wang

DOI: 10.2147/OTT.S96278

关键词: Messenger RNAGene expressionReverse transcription polymerase chain reactionGliomaBiologyLong non-coding RNAMolecular biologySmall interfering RNAGene knockdownTemozolomide

摘要: Temozolomide (TMZ) is commonly used in glioma chemotherapy. However, a great clinical challenge for TMZ chemoresistance. H19 transcripts are recognized as long noncoding RNAs, which potentially interact with chromatin-modifying complexes to regulate gene expression via epigenetic changes. Our data based on patients showed that the of was significantly upregulated TMZ-resistant tumors compared TMZ-sensitive tumors. To determine function glioma, cell lines U87 and U251 were exposed establish clones U87(TMZ) U251(TMZ). In U251(TMZ), level increased wild-type or nonresistant clones, determined by real-time quantitative reverse transcription polymerase chain reaction. Concomitant treatment small interfering RNA specifically targeting resistant resulted decreased IC50 values TMZ, apoptotic rates than control RNA-treated cells. This also evident PARP cleavage cells + si-H19. Furthermore, reduced altered major drug resistance genes, such MDR, MRP, ABCG2, both at mRNA protein levels. Taken together, these findings suggest plays an important role development resistance, may represent novel therapeutic target gliomas.

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