New insight into the CNC-bZIP member, NFE2L3, in human diseases

Our plain-English summary of New insight into the CNC-bZIP member, NFE2L3, in human diseases, by G. Xiong, J. Li, F. Yao, et al (Frontiers in Cell and Developmental Biology, 2024).

The study

• Authors: G. Xiong, J. Li, F. Yao, F. Yang, Y. Xiang
• Journal: Frontiers in Cell and Developmental Biology
• Published: 2024;12:1430486
• Type of article: Review
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Nuclear factor erythroid 2 (NF-E2)-related factor 3 (NFE2L3), a member of the CNC-bZIP subfamily and widely found in a variety of tissues, is an endoplasmic reticulum (ER) membrane-anchored transcription factor that can be released from the ER and moved into the nucleus to bind the promoter region to regulate a series of target genes involved in antioxidant, inflammatory responses, and cell cycle regulation in response to extracellular or intracellular stress. Recent research, particularly in the past 5 years, has shed light on NFE2L3's participation in diverse biological processes, including cell differentiation, inflammatory responses, lipid homeostasis, immune responses, and tumor growth. Notably, NFE2L3 has been identified as a key player in the development and prognosis of multiple cancers including colorectal cancer, thyroid cancer, breast cancer, hepatocellular carcinoma, gastric cancer, renal cancer, bladder cancer, esophageal squamous cell carcinoma, T cell lymphoblastic lymphoma, pancreatic cancer, and squamous cell carcinoma. Furthermore, research has linked NFE2L3 to other cancers such as lung adenocarcinoma, malignant pleural mesothelioma, ovarian cancer, glioblastoma multiforme, and laryngeal carcinoma, indicating its potential as a target for innovative cancer treatment approaches. Therefore, to gain a better understanding of the role of NFE2L3 in disease, this review offers insights into the discovery, structure, function, and recent advancements in the study of NFE2L3 to lay the groundwork for the development of NFE2L3-targeted cancer therapies.

Copyright © 2024 Xiong, Li, Yao, Yang and Xiang.

In plain English

This article was a review, not an original study. The authors summarized published research on NFE2L3 (also called NRF3), a protein that switches genes on and off inside cells. They covered its discovery, structure, regulation, and roles in processes such as oxidative stress, inflammation, fat handling, protein balance and cell development, then reviewed studies of NFE2L3 in cancer. According to the studies reviewed, high NFE2L3 levels promoted cancer in most tumor types. The protein appeared to hold back tumor progression in T cell lymphoblastic lymphoma, skin squamous cell carcinoma and some breast cancers. Malignant pleural mesothelioma appeared only briefly, in lists of cancers, and the only source cited for it was a separate study by Wang and colleagues (2022). It was listed among several cancers where RNA sequencing data analyses suggested a possible link between abnormal NFE2L3 levels and prognosis. The authors said such findings still need to be tested by changing NFE2L3 levels in experiments. The article did not discuss asbestos. The authors concluded that NFE2L3 is a promising target for tumor treatment, while noting that research on it is at an early stage.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published research on the gene and protein NFE2L3
• Who was studied: No study population of its own. The authors reviewed published research on NFE2L3, with emphasis on work from roughly the past 5 years.
• Exposure: None. The article does not study or mention asbestos or any fiber exposure.
• Main results:
  • From the research reviewed, the authors described NFE2L3 as playing a role in cellular processes including oxidative stress, the inflammatory response, lipid homeostasis, proteostasis and cell differentiation.
  • According to the studies reviewed, highly expressed NFE2L3 promotes cancer in most tumors. In T cell lymphoblastic lymphoma, skin squamous cell carcinoma and some breast cancers, it inhibits tumor progression.
  • In the introduction, malignant pleural mesothelioma was listed among other cancers that studies have linked to NFE2L3. The source cited was a separate study by Wang et al. (2022).
  • In the later discussion, malignant pleural mesothelioma was listed among several cancers in which reports based on RNA sequencing data analysis, again citing Wang et al. (2022), indicated a potential correlation between abnormal NFE2L3 expression and prognosis.
• The authors' conclusion: The authors concluded that NFE2L3 is a promising target for tumor treatment, because earlier studies linked it to poor prognosis and changing its expression could potentially slow tumor progression.
• Limitations the authors state:
  • The authors stated that research on NFE2L3 is at an early stage and that many aspects have not yet been explored.
  • The authors stated that the links to cancers found through RNA sequencing data analysis, including malignant pleural mesothelioma, need to be validated by modulating NFE2L3 expression in experiments.
  • The authors noted that the exact mechanism by which NFE2L3 regulates oxidative stress remains unclear.

Topics

Medical terms in this study, explained in our Lexicon: Prognosis, Colorectal Cancer, Carcinoma, Stomach Cancer, Squamous Cell Carcinoma, Lung Adenocarcinoma, Pleural Mesothelioma, Ovarian Cancer.

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