Abstract
Glioblastoma (GBM) is the most common and aggressive malignant brain tumor with high morbidity and mortality. Human telomerase reverse transcriptase (hTERT), the catalytic subunit of human telomerase, is overexpressed in most cancers including GBM. It is well known that hTERT can compensate telomere shortening to immortalize cells. However, in addition to the canonical function, hTERT has the roles beyond canonical telomere maintenance. To further understand the effects of hTERT on glioblastoma progression, we investigated the role of hTERT in regulating autophagy—a conserved pathway, by which cells deliver cellular organic material and impaired organelles to the lysosomes for degradation and recycle these cargos to produce energy under a stressful condition. Our results showed that downregulation of hTERT impaired autophagy levels by suppressing BECN1/beclin-1 and induced an increase of reactive oxygen species (ROS), which resulted in cell death ultimately. On the contrary, overexpression of BECN1 or treating cells with the antioxidant N-acetylcysteine (NAC) could restore the survival of hTERT knockdown cells. Our study will provide an additional basis of telomerase-targeting therapy for future clinical anticancer treatment.
Highlights
Glioblastoma (GBM) is classified as grade IV glioma by the World Health Organization and accounts for about 20% of all brain tumors
We investigated the role of telomerase reverse transcriptase (TERT) in regulating reactive oxygen species (ROS) and autophagy, and the results showed that downregulation of Human telomerase reverse transcriptase (hTERT) can impair autophagy levels by suppressing BECN1 and lead to an increase of ROS, which resulted in cell death
By searching the GEPIA database, we found that hTERT mRNA levels were higher in lowgrade gliomas and glioblastoma (Grade IV glioma) than their corresponding normal tissues
Summary
Glioblastoma (GBM) is classified as grade IV glioma by the World Health Organization and accounts for about 20% of all brain tumors. Despite the improvement of medical technology and the rigorous treatment that patients received, it is still difficult to remove GBM tumors by surgical resection due to their invasion to the surrounding tissues. Recurrence often occurs in GBM patients, and the median survival is less than two years after diagnosis [2,3,4]. According to the 2016 WHO classification, increasing evidence demonstrated the genetic heterogeneity of GBM [5]. Even within a single glioblastoma, a combination of treatments may be required for different cell subtypes, greatly exacerbating the difficulty of treating this type of tumor
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