Journal
CANCER SCIENCE
Volume 113, Issue 8, Pages 2681-2692Publisher
WILEY
DOI: 10.1111/cas.15387
Keywords
chemoresistance; glioma; lncRNA XLOC; Sp1; temozolomide
Categories
Funding
- National Natural Science Foundation of China [82073193, 82003179, 81874079]
- Natural Science Foundation of Guangdong Province [2017A030308001, 2018A030310422]
- Guangdong Provincial Clinical Medical Centre for Neurosurgery [2013B020400005]
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The study identified the important role of the XLOC/Sp1/PIK3R2/PI3K/AKT axis in GBM TMZ resistance. XLOC was found to regulate TMZ resistance, cell proliferation, and apoptosis in GBM.
The discovery of long noncoding RNAs (lncRNAs) has improved the understanding of development and progression in various cancer subtypes. However, the role of lncRNAs in temozolomide (TMZ) resistance in glioblastoma multiforme (GBM) remains largely undefined. In this present study, the differential expression of lncRNAs was identified between U87 and U87 TMZ-resistant (TR) cells. lncRNA XLOC013218 (XLOC) was drastically upregulated in TR cells and was associated with poor prognosis in glioma. Overexpression of XLOC markedly increased TMZ resistance, promoted proliferation, and inhibited apoptosis in vitro and in vivo. In addition, RNA-seq analysis and gain-of-function or loss-of-function studies revealed that PIK3R2 was the potential target of XLOC. Mechanistically, XLOC recruited specificity protein 1 (Sp1) transcription factor and promoted the binding of Sp1 to the promoters of PIK3R2, which elevated the expression of PIK3R2 in both mRNA and protein levels. Finally, PIK3R2-mediated activation of the PI3K/AKT signaling pathway promoted TMZ resistance and cell proliferation, but inhibited cell apoptosis. In conclusion, these data highlight the vital role of the XLOC/Sp1/PIK3R2/PI3K/AKT axis in GBM TMZ resistance.
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