Enhancing miR-132 expression by aryl hydrocarbon receptor attenuates tumorigenesis associated with chronic colitis

Abdullah, Alzahrani; Hanieh, Hamza; Ibrahim, Hairul-Islam Mohamed; Mohafez, Omar Mahmoud Mohamed; Shehata, Tamer M.; Ismail, Mohammad Bani; Alfwuaires, Manal

doi:10.1016/j.intimp.2017.09.015

Cited by 29 publications

(25 citation statements)

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“…AhR and its effects on the NLRP3 inflammasome and colitis have been predominantly studied using wild-type (AhR +/+ ), AhR knockout (AhR −/− ) and heterozygous (AhR −/+ ) mouse models that have been chemically induced with intestinal inflammation; by using 2,4,6-trinitrobenzene sulphonic acid (TNBS) or dextran sulphate sodium (DSS), and CAC; by using azoxymethane (AOM or AOM/DSS) [70]. Several studies have determined that AhR exhibits protective effects during intestinal inflammation; with TCDD-treated and FICZ-treated mice ameliorating colitis severity, which were determined from corrected weight loss, reduced colitis symptoms and recover periods [159][160][161][162][163]. These reversed colitis effects were due to a change in their cytokine environment, with AhR-activated mice having a reduction in the expression of pro-inflammatory mediators; such as IL-6, IL-12, IL-17, IFN-c, MCP-1, exotaxin-1 and TNF-α, but an increase in IL-22 and TGF-β [159,162,163].…”

Section: Role Of Mouse Models In the Investigation Of Ahr In Maintainmentioning

confidence: 99%

“…Several studies have determined that AhR exhibits protective effects during intestinal inflammation; with TCDD-treated and FICZ-treated mice ameliorating colitis severity, which were determined from corrected weight loss, reduced colitis symptoms and recover periods [159][160][161][162][163]. These reversed colitis effects were due to a change in their cytokine environment, with AhR-activated mice having a reduction in the expression of pro-inflammatory mediators; such as IL-6, IL-12, IL-17, IFN-c, MCP-1, exotaxin-1 and TNF-α, but an increase in IL-22 and TGF-β [159,162,163]. The results from Monteleone et al supports this notion with FICZ-treated TNBS-induced mice showing reversed colitis symptoms while also showing that colitis symptoms were enhanced when the mice were treated with AhR antagonists [164].…”

Section: Role Of Mouse Models In the Investigation Of Ahr In Maintainmentioning

confidence: 99%

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Does NLRP3 Inflammasome and Aryl Hydrocarbon Receptor Play an Interlinked Role in Bowel Inflammation and Colitis-Associated Colorectal Cancer?

2020

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Inflammation is a hallmark in many forms of cancer; with colitis-associated colorectal cancer (CAC) being a progressive intestinal inflammation due to inflammatory bowel disease (IBD). While this is an exemplification of the negatives of inflammation, it is just as crucial to have some degree of the inflammatory process to maintain a healthy immune system. A pivotal component in the maintenance of such intestinal homeostasis is the innate immunity component, inflammasomes. Inflammasomes are large, cytosolic protein complexes formed following stimulation of microbial and stress signals that lead to the expression of pro-inflammatory cytokines. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome has been extensively studied in part due to its strong association with colitis and CAC. The aryl hydrocarbon receptor (AhR) has recently been acknowledged for its connection to the immune system aside from its role as an environmental sensor. AhR has been described to play a role in the inhibition of the NLRP3 inflammasome activation pathway. This review will summarise the signalling pathways of both the NLRP3 inflammasome and AhR; as well as new-found links between these two signalling pathways in intestinal immunity and some potential therapeutic agents that have been found to take advantage of this link in the treatment of colitis and CAC.

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Section: Role Of Mouse Models In the Investigation Of Ahr In Maintainmentioning

confidence: 99%

Section: Role Of Mouse Models In the Investigation Of Ahr In Maintainmentioning

confidence: 99%

Does NLRP3 Inflammasome and Aryl Hydrocarbon Receptor Play an Interlinked Role in Bowel Inflammation and Colitis-Associated Colorectal Cancer?

2020

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“…AHR-mediated carcinogenesis with the disruption of eicosanoid homeostasis as reviewed recently [30], is involved in breast cancer [328,329], colitis associated colon cancer through miR-132 expression after AHR activation by TCDD [330]. B[a]P induces AHR-dependent IL-10 increase with chronic inflammation [331] and AHR is involved in inflammatory fibrosis of the pancreas [332] and the liver [333].…”

Section: Aryl Hydrocarbon Receptor (Ahr)mentioning

confidence: 99%

Transition from normal to cancerous cell by precancerous niche (PCN) induced chronic cell-matrix stress

Brücher

Jamall

2019

4open

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The attempt to restore homeostasis, once disrupted, such that complex signaling, crosstalk between ubiquitous proteins, and a diverse range of pathways gone awry is near impossible, especially in the presence of an ongoing pathogenic stimuli with incessant inflammation. This persistent inflammation, when unresolved, induces fibrosis with consequent remodeling of the extracellular matrix (ECM) which leads to the formation of the precancerous niche (PCN), the tipping point in the transition of normal to cancerous cells. Thus, the sustained disruption of homeostasis when confronted with limited adaptation capabilities either of cells or of the surrounding matrix and faced with chronic stress in the tissue microenvironment results in an escape strategy which, if unsuccessful, causes cells, tissue, or the organism to become unable to recover over the long term. All conditions necessary for cell–cell transition such as deregulation of cell–cell complexes, decrease in the stability of adherens junctions, together with the apical-basal polarity, and the loss of the cytoskeletal architecture occurs as a cascade of events inducing inappropriate and diverse signaling pathways and crosstalk. In biology, the transition of one cell type to another and the transition from one cell function to another is incompletely understood mechanistically, but within the context of embryogenesis and morphogenesis is acknowledged as a physiologically routine event. The constant stress that can result in the development of the PCN leads to a chronic stress escape strategy (CSES) which, if unsuccessful, eventually triggers a normal cell- to-cancer cell- transition (NCCCT).

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“…Within these regulatory networks, microRNAs (miRs) can interact with downstream target genes, some of which have been linked to cancer progression (9). A recent study demonstrated that increased levels of miR-132 by aryl hydrocarbon receptor attenuate tumorigenesis associated with chronic colitis (10). Furthermore, it was revealed that miR-141 was involved in the pathogenesis of ulcerative colitis by targeting C-X-C motif chemokine ligand 5 (11).…”

Section: Introductionmentioning

confidence: 99%

Peripheral blood miR‑372 as a biomarker for ulcerative colitis via direct targeting of NLRP12

Shen

2019

Exp Ther Med

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The present study aimed to investigate the expression pattern and underlying mechanism of microRNA-372 (miR-372) in the progression of ulcerative colitis (UC). Reverse transcription-quantitative polymerase chain reaction was used to measure miR-372 expression levels in the blood and colonic mucosa tissue samples from patients with UC. The present study demonstrated that levels of miR-372 were significantly increased in the blood and colonic mucosa tissue samples from patients with UC compared with healthy controls. Furthermore, the level of serum miR-372 was positively correlated with the level of serum c-reactive protein. Receiver operating characteristic analysis indicated that levels of miR-372 detected in serum and tissue samples could be used to screen for patients with UC from healthy controls. These results indicated a potential role of miR-372 as a diagnostic marker and therapeutic target for patients with UC. Furthermore, a conserved miR-372 binding site in the 3'untranslated region of the NLR family pyrin domain containing 12 (NLRP12) was identified. Dual luciferase assay demonstrated that overexpression of miR-372 significantly reduced the relative luciferase activity of pmirGLO-NLRP12-3'UTR compared with control pmirGLO. In addition, western blot analysis indicated that overexpression of miR-372 significantly decreased the protein expression level of NLRP12. Therefore it was hypothesized that miR-372 may promote the progression of UC by suppressing NLRP12 protein expression and thereby inducing the excessive production of inflammatory cytokines. In conclusion, high levels of miR-372 detected in peripheral blood samples may serve a role as a potential biomarker to screen potential patients with UC from healthy controls.

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Enhancing miR-132 expression by aryl hydrocarbon receptor attenuates tumorigenesis associated with chronic colitis

Abstract: Our findings identify miR-132 as a new molecule implicated in CAC pathogenesis, and reveal that miR-132 mediates the ameliorating effects of TCDD on CAC, suggesting miR-132 as a promising therapeutic candidate to control autoimmune inflammation and tumorigenesis in CAC patients.

Cited by 29 publications

References 50 publications

Does NLRP3 Inflammasome and Aryl Hydrocarbon Receptor Play an Interlinked Role in Bowel Inflammation and Colitis-Associated Colorectal Cancer?

Does NLRP3 Inflammasome and Aryl Hydrocarbon Receptor Play an Interlinked Role in Bowel Inflammation and Colitis-Associated Colorectal Cancer?

Transition from normal to cancerous cell by precancerous niche (PCN) induced chronic cell-matrix stress

Peripheral blood miR‑372 as a biomarker for ulcerative colitis via direct targeting of NLRP12

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