KHDRBS3 facilitates self-renewal and temozolomide resistance of glioblastoma cell lines

Abstract

AbstractGlioblastoma is a deadly tumor which possesses glioblastoma stem cell populations involved in temozolomide resistance. To gain insight into the mechanisms of self-renewing and therapy-resistant cancer stem cells, subcellular proteomics was utilized to identify proteins whose expression is enriched in U251-derived glioblastoma stem-like cells. The RNA binding protein KHDRBS3 was successfully identified as a gene up-regulated in the cancer stem cell population compared with its differentiated derivatives. Depletion of KHDRBS3 by RNA silencing led to a decrease in cell proliferation, neurosphere formation, migration, and expression of genes involved in glioblastoma stemness. Importantly, temozolomide sensitivity can be induced by the gene knockdown. Collectively, our results highlight KHDRBS3 as a novel factor associated with self-renewal of glioblastoma stem-like cells and temozolomide resistance. As a consequence, targeting KHDRBS3 may help eradicate glioblastoma stem-like cells.