The aim of this study was to investigate the association between the expression of HOTAIR and the grades of gliomas, and to explore its possible mechanism, as well as to evaluate the value of HOTAIR applied in predicting the grades of gliomas.
It has been previously reported that the lincRNA HOTAIR mediates recruitment of polycomb repressive complex 2 (PRC2) leading to aberrant transcriptional silencing of tumor suppressor genes in glioma and breast cancer.
Taken together, our study clarified that the HOTAIR/miR-126/GLS pathway is involved in glioma progression and may potentially serve as a target for glioma therapy.
Our findings support that down-regulation of HOTAIR could inhibit cell proliferation, promote cell apoptosis as well as suppress cell invasion and migration in the progression of glioma.
Our study also showed that HOTAIR was present in the glioma cell culture supernatant and was protected by membranes, suggesting that HOTAIR may affect glioma angiogenesis not only via regulation of VEGFA expression in the glioma cells, but also by transmission into endothelial cells via glioma cell-derived extracellular vesicles.
Our results suggest that HOTAIR SNPs rs920778 and rs12826786 do not play a significant role in glioma susceptibility, but may be important prognostic factors in anaplastic oligodendroglioma patients.
Finally, both overexpression of miR-141 and knockdown of HOTAIR in a mouse model of human glioma resulted in significant reduction of tumor growth in vivo.
Taken together, knockdown of HOTAIR up-regulated miR-326 expression, and further inducing the decreased expression of FGF1, these results provided a comprehensive analysis of HOTAIR-miR-326-FGF1 axis in human glioma and provided a new potential therapeutic strategy for glioma treatment.