1. Academic Validation
  2. Transcription factor Nrf2 binds to circRNAPIBF1 to regulate SOD2 in lung adenocarcinoma progression

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

  • Mol Carcinog. 2022 Oct 4. doi: 10.1002/mc.23468.
Zuxiong Zhang 1 2 3 Qianshun Chen 1 4 Chen Huang 4 Dingyu Rao 2 3 Chengpeng Sang 2 3 Shenyu Zhu 2 3 Liang Gu 2 3 Chunfa Xie 2 3 Zhixian Tang 2 3 Xunyu Xu 1 4
Affiliations

Affiliations

  • 1 Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, P.R. China.
  • 2 Department of Thoracic Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, P.R. China.
  • 3 Ganzhou Key Lab of Brain Injury & Brain Protection, Ganzhou, Jiangxi, P.R. China.
  • 4 Department of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian, P.R. China.
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.

Keywords

CircRNA_PIBF1; Nrf2; SOD2; lung adenocarcinoma; pyroptosis.

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