Knockdown of arsenic resistance protein 2 inhibits human glioblastoma cell proliferation through the MAPK/ERK pathway.

Abstract

It is generally known that glioblastoma is the most common primary malignant brain tumor and that it is highly aggressive and deadly. Although surgical and pharmacological therapies have made long-term progress, glioblastoma remains extremely lethal and has an uncommonly low survival rate. Therefore, further elucidation of the molecular mechanisms of glioblastoma initiation and its pathological processes are urgent. Arsenic resistance protein 2 (Ars2) is a highly conserved gene, and it has been found to play an important role in microRNA biosynthesis and cell proliferation in recent years. Furthermore, absence of Ars2 results in developmental death in Drosophila, zebrafish and mice. However, there are few studies on the role of Ars2 in regulating tumor development, and the mechanism of its action is mostly unknown. In the present study, we revealed that Ars2 is involved in glioblastoma proliferation and we identified a potential mechanistic role for it in cell cycle control. Our data demonstrated that Ars2 knockdown significantly repressed the proliferation and tumorigenesis abilities of glioblastoma cells in vitro and in vivo. Further investigation clarified that Ars2 deficiency inhibited the activation of the MAPK/ERK pathway, leading to cell cycle arrest in the G1 phase, resulting in suppression of cell proliferation. These findings support the conclusion that Ars2 is a key regulator of glioblastoma progression.