Transcription factor Nrf2 binds to circRNAPIBF1 to regulate SOD2 in lung adenocarcinoma progression

Abstract

Emerging evidence indicates that circular RNAs (circRNAs) play important roles in disease development, especially in cancers. Analysis of circRNA expression microarrays from the Gene Expression Omnibus database revealed that circPIBF1 was highly upregulated in lung adenocarcinoma (LUAD). The main aim of this study was to probe the function of circPIBF1 in pyroptosis of LUAD cells and the signal transduction pathways involved. CircPIBF1 was significantly overexpressed in LUAD and was related to the dismal prognosis of patients with LUAD. CircPIBF1 could bind to nuclear factor erythroid 2‐related factor 2 (Nrf2), which further promoted the expression of superoxide dismutase 2 (SOD2). In addition, Nrf2 was also observed to recruit histone acetyltransferase E1A binding protein p300 (EP300) to enhance H3K27ac modification of SOD2, thus modulating the Nrf2‐Keap1 signaling pathway. Moreover, we found that knockdown of circPIBF1 significantly suppressed the expression of SOD2 in cells and LUAD cell growth, while enhanced the expression of pyroptosis‐related factors, which were further reversed by overexpression of SOD2 or EP300. Collectively, our findings suggest a direct involvement of circPIBF1 in pyroptosis‐related LUAD carcinogenesis and implicate a role of Nrf2/EP300/SOD2 signaling in this process.

FOXC2‐induced circCASK aggravates colorectal cancer progression by upregulating SIX1 expression

“…It has been reported that circRNA expression is regulated by transcription factors 18–20 . To identify the upstream mechanisms of circCASK, we explored the NCBI (https://www.ncbi.nlm.nih.gov/), UCSC (http://genome.ucsc.edu/), and JASPAR (http://jaspar.genereg.net/) datasets.…”

“…In addition, we further investigated the upstream mechanisms of circCASK by exploring potential transcription factors that could regulate circRNAs expression in various cells 18–20 . By generating knockdown or overexpression cell models, we found that FOXC2 positively regulated circCASK expression in CRC cells.…”

“…It has been reported that circRNA expression is regulated by transcription factors. [18][19][20] To identify the upstream mechanisms of circCASK, we explored the NCBI (https:// www.ncbi.nlm.nih.gov/), UCSC (http://genome.ucsc.edu/ ), and JASPAR (http://jaspar.genereg.net/) datasets. Seven transcription factors (HOXB13, HOXD9, HOXA10, CDX4, CDX2, CDX1, and FOXC2) were identified as potential regulators of circCASK.…”

WDR23 mediates NRF2 proteostasis and cytoprotective capacity in the hippocampus

“…To test whether the increase in established NFE2L2/NRF2-regulated transcripts measured in Wdr23KO hippocampus resulted in an increase in steady state abundance of stress adaptation proteins, we quantified the steady state level of several proteins with roles in redox and oxidative stress resistance [45]. We noted an increase in the abundance of several proteins that mediate survival and protection from oxidative stress [46] in the Wdr23KO relative to WT; these include the glutathione peroxidase 4 (GPX4, Figure 6A-B ), glutathione S transferase 4 (GSTA4, Figure 6A,C ), aldehyde dehydrogenase 2 (ALDH2, Figure 6A,D ), and the manganese superoxide dismutase 2 [47] (SOD2, Figure 6E-F ). Intriguingly, we could not detect an increase in all proteins with known sensitivity to NFE2L2/NRF2 activation (Figure S6) suggesting a failure in the sensitivity of detection for these proteins or perhaps specificity to the WDR23-axis of regulation of NFE2L2/NRF2 in the hippocampus specifically, which will be of great future interest.…”