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

Serpin 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 of SERPINA1, but its effects on glioma cells remain unknown. In this study, we explored the functions of SERPINA1 in glioma tumorigenesis in vitro and then investigated whether NQO1 affects the protein expression of SERPINA1 and its mRNA level. The results showed that the translation of SERPINA1 was suppressed while its mRNA level had no significant changes under the condition of NQO1 silencing. Luciferase reporter assay and biotin pull-down assay further indicated that NQO1 bond with SERPINA1 3′ untranslated region. miR-1321 was also identified to target SERPINA1, repressing its mRNA and protein levels. SERPINA1 and NQO1 promoted glioma cell proliferation and suppressed cell apoptosis. Moreover, SERPINA1 rescued the effects of sh-NQO1 in glioma cell malignant phenotypes. In conclusion, our findings showed that oncogene NQO1 and antioncogene miR-1321 bind to oncogene SERPINA1 to affect proliferation and apoptosis of glioma cells, which can bring new solution of antitumor treatments for glioma in the future.

Keywords

• glioma
• serpina1
• nqo1
• rna-binding protein
• mir-1321