The NRF2 transcription factor plays a dual role in colorectal cancer : A systematic review

Background: Colorectal cancer is one of the most common cancers worldwide, and is influenced by the interplay of various factors, including a very strong genetic component. For instance, incorrect mitochondrial biogenesis is correlated with increased risk of developing colorectal cancer. Thus, it is important to understand the consequences of changes in both the expression and the correct function of the transcription factors that regulate mitochondrial biogenesis, namely NRF2. Objectives: The main objective of this paper is to characterise the relationship between NRF2 and colorectal cancer by compiling data from an exhaustive literature search. Methods: Information was obtained by defining specific search terms and searching in several databases. After a strict selection procedure, data were tabulated and the relationships between articles were assessed by measuring heterogeneity and by constructing conceptual maps. Results and discussion: We found a general consensus in the literature that the presence of oxidizing agents as well as the inhibition of the NRF2 repressor Keap1 maintain NRF2 expression at basal levels. This predominantly exerts a cytoprotective effect on cells and decreases risk of colorectal cancer. However, if NRF2 is inhibited, protection against external agents disappears and risk of colorectal cancer increases. Interestingly, colorectal cancer risk is also increased when NRF2 becomes overexpressed. In this case, the increased risk arises from NRF2-induced inflammation and resistance to chemotherapy. Conclusion: The proper basal function of NRF2 and Keap1 are essential for preventing oncogenic processes in the colon. Consequently, any disruption to the expression of these genes can promote the genesis and progression of colon cancer

PoDA algorithm: Predictive pathways in colorectal cancer

SOCO’17-CISIS’17-ICEUTE’17 (León. 2017

The NRF2 transcription factor plays a dual role in colorectal cancer: A systematic review

<div><p>Background</p><p>Colorectal cancer is one of the most common cancers worldwide, and is influenced by the interplay of various factors, including a very strong genetic component. For instance, incorrect mitochondrial biogenesis is correlated with increased risk of developing colorectal cancer. Thus, it is important to understand the consequences of changes in both the expression and the correct function of the transcription factors that regulate mitochondrial biogenesis, namely NRF2.</p><p>Objectives</p><p>The main objective of this paper is to characterise the relationship between NRF2 and colorectal cancer by compiling data from an exhaustive literature search.</p><p>Methods</p><p>Information was obtained by defining specific search terms and searching in several databases. After a strict selection procedure, data were tabulated and the relationships between articles were assessed by measuring heterogeneity and by constructing conceptual maps.</p><p>Results and discussion</p><p>We found a general consensus in the literature that the presence of oxidizing agents as well as the inhibition of the NRF2 repressor Keap1 maintain NRF2 expression at basal levels. This predominantly exerts a cytoprotective effect on cells and decreases risk of colorectal cancer. However, if NRF2 is inhibited, protection against external agents disappears and risk of colorectal cancer increases. Interestingly, colorectal cancer risk is also increased when NRF2 becomes overexpressed. In this case, the increased risk arises from NRF2-induced inflammation and resistance to chemotherapy.</p><p>Conclusion</p><p>The proper basal function of NRF2 and Keap1 are essential for preventing oncogenic processes in the colon. Consequently, any disruption to the expression of these genes can promote the genesis and progression of colon cancer.</p></div

Heterogeneity assessment.

<p>This graph evaluates if certain features are present in the articles included in this review.</p

Overexpression of NRF2 and the relation with CRC.

<p>Constitutive activation of NRF2 promotes a serie of events that lead to an increased risk of CRC.</p

Summarized table about the included reports.

<p>Summarized table about the included reports.</p

PRISMA 2009 flow diagram.

<p>This flow chart shows the process of selecting articles included in the qualitative systematic review.</p

Simplified diagram of the activation of NRF2 transcription factor via ROS.

<p>When ROS is acumulated, NRF2 is released from Keap1 and heterodimerizes with Small Mafs. In this way, it binds to AREs and the transcription of antioxidant and cytoprotective genes occurs.</p

Inhibition of NRF2 and the relation with CRC.

<p>Inhibition or permanently silencing of NRF2 induce the formation of aberrant crypts and other typical processes related to the increased risk of CRC such as rectal bleeding or ulcerative colitis.</p