NRF1-regulated CircNSUN2 promotes lymphoma progression through activating Wnt signaling pathway via stabilizing HMGA1

Abstract

ABSTRACT Lymphoma is the malignant tumor in the lymphatic system. Circular RNAs (circRNAs) are non-coding RNAs with closed structure, which have been reported to perform critical functions in various tumor progressions. However, the role of circNSUN2 in lymphoma has not been well explored. Quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR) assay was performed to test the expression of circNSUN2 in malignant lymphoma tissues and normal lymph tissues, as well as in human peripheral blood lymphocyte cell line and malignant lymphoma cell lines. Cell counting kit-8 (CCK-8) assay and Transwell assays were used to evaluate the function of circNSUN2 on lymphoma cell proliferation, migration and invasion. DNA pull-down assay, chromatin immunoprecipitation (ChIP) and luciferase reporter assay were employed to test the interaction between circNSUN2 and NRF1. TOP/FOP flash reporter assay was performed to detect influence of circNSUN2 on Wnt pathway. Luciferase reporter assay and RNA pull-down assay were performed to explore interaction between HMGA1 and circNSUN2 through Wnt pathway. CircNSUN2 expression was abnormally high in malignant lymphoma tissues and cell lines. CircNSUN2 inhibition could reduce proliferation and invasion of lymphoma. Bioinformatic analysis, DNA pull-down, ChIP and luciferase reporter experiments confirmed that circNSUN2 could be modulated by transcription factor NRF1. Through RT-qPCR, western blot and luciferase reporter assays, circNSUN2 was proved to influence Wnt pathway by modulating HMGA1. CircNSUN2 regulated by transcription factor NRF1 could promote lymphoma progression through activating Wnt pathway via stabilizing HMGA1.