Serpin family A member 1 is an oncogene in glioma and its translation is enhanced by NAD(P)H quinone dehydrogenase 1 through RNA-binding activity

Abstract

AbstractSerpin family A member 1 (SERPINA1) is expressed abundantly in gliomas and can predict unfavorable prognosis of patients with glioma. Studies have shown that nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (NQO1) can promote the proliferation of glioblastoma multiforme cells and enhance the expression ofSERPINA1, but its effects on glioma cells remain unknown. In this study, we explored the functions ofSERPINA1in glioma tumorigenesisin vitroand then investigated whetherNQO1affects the protein expression ofSERPINA1and its mRNA level. The results showed that the translation ofSERPINA1was suppressed while its mRNA level had no significant changes under the condition ofNQO1silencing. Luciferase reporter assay and biotin pull-down assay further indicated thatNQO1bond withSERPINA13′ untranslated region. miR-1321 was also identified to targetSERPINA1, repressing its mRNA and protein levels. SERPINA1andNQO1promoted glioma cell proliferation and suppressed cell apoptosis. Moreover,SERPINA1rescued the effects of sh-NQO1 in glioma cell malignant phenotypes. In conclusion, our findings showed that oncogeneNQO1and antioncogene miR-1321 bind to oncogeneSERPINA1to affect proliferation and apoptosis of glioma cells, which can bring new solution of antitumor treatments for glioma in the future.