Knockdown of neurotrophin receptor-interacting melanoma-associated antigen homolog inhibits acute myeloid leukemia cell growth via the ERK pathway

Abstract

Neurotrophin receptor-interacting melanoma-associated antigen homolog (NRAGE), a type II melanoma-associated antigen, plays a critical role in cell processes that are involved in the tumorigenesis of various cancers. However, the effect of NRAGE on acute myeloid leukemia (AML) is rarely reported. The expression of NRAGE in AML tissues and the survival rates between different AML groups were obtained from the GEPIA tool. Human AML cell lines were cultured and transfected with siRNA targeting NRAGE. The ability of AML cells to proliferate and cell cycle were examined. Western blotting was performed to detect the activity of the extracellular signal-regulated kinase (ERK) signaling pathway in AML cells. NRAGE expression was enhanced in AML tissues relative to control tissues, and the high NRAGE expression in AML patients is associated with a poor prognosis. The capacity of AML cells to survive and proliferate was significantly decreased and its cell cycle was arrested at the G1 phase after NRAGE was silenced. Furthermore, silencing NRAGE induced the inactivation of the ERK signaling pathway. Furthermore, supplement of tert-Butylhydroquinone, an ERK activator, improved the reduced ability of AML cell survival and proliferation as well as cell cycle arrest induced by NRAGE knockdown. In this study, NRAGE was identified as a tumor promoter in AML, which had an effect on cell proliferation, cell survival, and cell cycle through the ERK signaling pathway in AML cells.

Keywords

• acute myeloid leukemia
• cell cycle
• cell growth
• extracellular signal-regulated kinase signaling pathway
• neurotrophin receptor-interacting melanoma-associated antigen homolog