Hypoxia-mediated mitochondria apoptosis inhibition induces temozolomide treatment resistance through miR-26a/Bad/Bax axis.

ABSTRACT: Glioblastoma multiforme (GBM) is one of the most hypoxic tumors of the central nervous system. Although temozolomide (TMZ) is an effective clinical agent in the GBM therapy, the hypoxic microenvironment remains a major barrier in glioma chemotherapy resistance, and the underlying mechanisms are poorly understood. Here, we find hypoxia can induce the protective response to mitochondrion via HIF-1α-mediated miR-26a upregulation which is associated with TMZ resistance in vitro and in vivo. Further, we demonstrated that HIF-1α/miR-26a axis strengthened the acquisition of TMZ resistance through prevention of Bax and Bad in mitochondria dysfunction in GBM. In addition, miR-26a expression levels negatively correlate with Bax, Bad levels, and GBM progression; but highly correlate with HIF-1α level

SUBMITTER: Ge X 

PROVIDER: S-EPMC6233226 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature