AHR expression

Sex and loss of IEC AhR also resulted in changes in microbial populations in the gut. Collectively, these data suggest that the formation of TLTs in the colon is influenced by sex and AhR expression in IECs.

Further, after being pre-treated with AhR antagonist CH223191, the inhibition of TCDD on A172 cells migration was not changed, indicating that the effect of TCDD on A172 cells is not dependent on AhR activation. By transcriptome sequencing analysis, we propose dysregulation of the expression of certain migration-related genes, such as IL6, IL1B, CXCL8, FOS, SYK, and PTGS2 involved in cytokines, MAPK, NF-κB, and IL-17 signaling pathways, as potential AhR-independent mechanisms that mediate the inhibition of TCDD migration in A172 cells.

Overall, these results confirm that smoking has an effect on the miRNA expression profile. This should be taken into account when searching for new diagnostic and therapeutic targets for NSCLC.

Conversely, reducing AHR expression in AML cells decreases cytarabine resistance. These findings deepen our understanding of the AHR signaling pathway's involvement in AML.

In vivo, 3FPP suppressed tumor growth and activated AhR signaling in an orthotopic mouse model. In conclusion, our results introduce the fused pyrazolopyridine 3FPP as a novel AhR agonist with AhR-specific anti-breast cancer potential in vitro and in vivo.

At the same time, it increased DNA POLβ protein expression, which indicates increased DNA repair, thus causing a chemopreventive effect. These results provide evidence for the chemopreventive effects of DATS in breast cancer prevention.

B[a]P/DATS's co-treatment (CoTx) inhibited cell proliferation, clonogenic formation, ROS formation, AhR protein expression, and 8-OHdG levels compared with B[a]P alone and attenuated all the above-mentioned B[a]P-induced changes in protein expression, causing a chemopreventive effect. This study demonstrates, for the first time, that DATS prevents premalignant breast cells from undergoing B[a]P-induced neoplastic transformation, thus providing more evidence for its chemopreventive effects in breast cancer.

Both AhR agonists and antagonists may be effective in inhibiting critical activities of breast cancer. The present review evaluates the role and underlying mechanisms of AhR and its ligands in breast cancer and demonstrates the potential of exploiting AhR as a novel target for breast cancer therapy.

Th22, Th17, Th1, and Th2 subsets may play an essential role in BC patients. Th22, Th17, Th1, and Th2 cells may have potential significance to be used as clinical markers in BC patients with different molecular classification. Th22 cells may have potential value in BC patients' outcomes prediction, providing clinical value.

These findings identify AhR inhibition as a novel therapeutic approach to overcome immune resistance in various types of cancers.

Twelve mice were divided into dimethyl sulfoxide (DMSO) alone group, PTH 6+DMSO group, MG-132 alone group, and PTH 6+MG-132 group, with 3 mice in each group... Ubiquitin degradation of AhR in PMs of mice after major trauma results in decreased protein expression of AhR. Increasing the expression of AhR in post-traumatic macrophages can reduce the expressions of LPS-induced inflammatory cytokines IL-6 and TNF-α, and improve the bactericidal ability of macrophages after trauma.

The immune response disbalance with regards of cytokine production, monocyte count and function as well as PD1 expression in PBMC’s is related to low AhR gene expression. This might explain the checkpoint inhibitor treatment failure in particular subset of patients (low AhR expression group).

Functional assays demonstrated changes in phagocytosis, nitric oxide production, and the expression of cytokines IL-1, IL-6, and IL-10. These findings indicate that AHR's expression level has a crucial role in immune dysregulation in PDAC and could be a potential target for early diagnostics and personalised therapeutics.

Therefore, we can conclude that increased mRNA levels of CYP24A1, AHR, CPEB4, TRIP13, and PIK3CA in blood samples withdrawn from colorectal cancer patients could be a biomarker for the disease.

In vivo, TDO2 expression positively correlated with the expression of genes crucial for leiomyoma growth. In summary, activation of the TDO2-kynurenine-AHR pathway selectively in mut-MED12 leiomyoma promotes tumor growth and may inform the future development of targeted treatments and precision medicine.

In conclusion, AHR and ELAVL1 interaction can form a negative feedback loop. By inhibiting AHR expression, PDAC cells become more susceptible to gemcitabine through the ELAVL1-DCK pathway.

Inhibition of AhR increases STING levels and reduces tumor growth under cisplatin or STING agonist treatment. Endogenous AhR ligands are mainly consisted of tryptophan (Trp) metabolites; dietary Trp restriction, blocking the key Trp metabolism rate-limiting enzyme IDO1 or inhibition of cellular Trp importation also show similar effect as AhR inhibition. Clinically, BC patients with higher intratumoral expression of AhR or stronger intratumoral Trp metabolism (higher IDO1 or Kyn levels) that lead to higher AhR activation show worse response rate to neoadjuvant chemotherapy (NAC).

Moreover, E2 showed a strong inhibitory effect on STAT3 expression and mild effect on NF-kB activity. These results suggest that fatty acids extracted from an endolichenic fungus can exert strong immunotherapeutic effects.

In order to determine therapeutic targeting of AhR in TNBC, we investigated the anti-cancer effects of the novel AhR ligand 11-chloro-7Hbenzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (11-Cl-BBQ), which belongs to a class of high affinity, rapidly metabolized AhR ligands called benzimidazoisoquinolines (BBQs). 11-Cl-BBQ induced AhR-dependent cancer-cell selective growth inhibition and strongly inhibited colony formation in TNBC cells.

Jdp2 plays a critical role in AhR promoter activation through the AhR-Jdp2-Nrf2 axis in a spatiotemporal manner. The AhR functions to maintain ROS balance and cell spreading, invasion, and cancer regression in a mouse model of mutant Kras-Trp53 pancreatic cancer. These findings provide new insights into the roles of Jdp2 in the homeostatic regulation of oxidative stress and in the antioxidation response in detoxification, inflammation, and cancer progression.

Interleukin 22 belongs to IFN-IL-10 cytokine family...The pathogenic and protective nature of the Th22 cells is modulated both by the site of infected tissue and the type of disease pathology. This review aims to discuss key features of IL-22 biology, comparisons between IL and 22 and IFN-γ and its role as a potential immune therapy target in different maladies.

In such cases, gemcitabine remains one the first-line drugs used for treatment [2] but the efficacy of the treatment can fall short due to PDAC tumour heterogeneity and its acquired resistance to said chemotherapy [3]... A direct relationship between AHR and ELAVL1 can be seen in PDAC. Moreover, by decreasing AHR expression it is possible to increase ELAVL1 shuttling from nucleus to cytoplasm which might contribute to PDAC cells responding better to chemotherapy.

This study showed negative PD1 gene expression correlation with AHR expression after indirect interactions with cancer cells in healthy participants PBMCs. Also, PBMCs co-cultivation with cancer cells initiated strong functional response and higher expression of inflammatory cytokines. These results show us different AHR relations with immunity response in healthy and cancer patients.

In vivo, TDO2 expression positively correlated with the expression of genes crucial for LM growth. Insummary, activation of the TDO2-kynurenine-AHR pathway selectively in mut-MED12 LM induces tumor growth and may inform the development of targeted treatments and precision medicine.

The expression levels of TMPRSS2 were found to correlate with nuclear AhR expression and with cancer stage in lung cancer patient tissue. Long-term exposure to PM2.5 could promote tumor progression in lung cancer through activation of EGFR and AhR to enhance the TMPRSS2-IL18 pathway.

In contrast, the AHR expression was diminished in the lung cancer tissues. Accordingly, the data from this study suggest that AHR has tumor suppressor-like activity for human lung cancer, and one of the carcinogenic mechanisms of arsenic is likely mediated by the inhibition of arsenic on the tumor suppressor-like activity of AHR.

Similarly, the mRNA levels of AhR, AMPs, and mucins were significantly increased in DSS+I3C-treated colon adenocarcinoma cells MC-38 (murine) and Caco2 (human) when compared to DSS-treated cells. To conclude, our findings demonstrate that I3C inhibits colitis primarily through AhR-mediated induction of AMPs and protective mucins, resulting in the enrichment of healthy gut microbiota (This work was supported in part by NIH grants R01ES030144, P01AT003961, P20GM103641, and R01AI123947, R01AI160896).

Our results suggest gut microbiota-derived metabolites as potential mediators of immunosuppression in the setting of premalignancy, which could increase cancer risk and be targets of cancer-preventing strategies.

we demonstrated that IL4I1 facilitated colorectal cancer progression and immunosuppression through tryptophan metabolism dependent on AHR activation.

All this makes us rethink the role of AhR in lung carcinogenesis and investigate the mechanisms of its activation by exogenous and endogenous ligands. This review highlights the current understanding of the functional features of AhR and its role in the LC pathogenesis.

Furthermore, FDI-6 was found to suppress tumorsphere formation via the AhR in MCF-7 cells and HepG2 human liver cancer cell line. On the basis of the findings of this study, we show that FDI-6, a FOXM1 inhibitor, functions as an AhR agonist, and suppresses tumorsphere formation via the AhR.

CRIPSR-cas9 knockout of individual genes revealed the requirement for both p53 and p27 for the AhR-mediated anti-proliferative effects. Our results identify 11-Cl-BBQ as a potential lung cancer therapeutic, highlight the feasibility of targeting AhR and provide important mechanistic insights into AhR-mediated-anticancer actions.

In vivo, carbidopa suppressed the growth of ER-positive breast cancer cells in mouse xenografts; this was associated with increased apoptosis and decreased cell proliferation. Carbidopa has therapeutic potential for ER-positive breast cancer either as a single agent or in combination with other standard chemotherapies.

The pharmacological inhibition of AhR, by CH223191, suppressed cell death signs and increased cell viability...Fascinatingly, during CCoV infection, a novel co-expression of NP and AhR expression was found. Taken together, our preliminary findings show that infection with CCoV activates AhR, and pharmacologic AhR inhibition reduces CCoV replication, identifying AhR as a possible candidate target for CCoV antiviral therapy.

We ranked the highest and lowest 10% expression levels of AHR by RNA expression (RPKM) across all samples in the Beat AML dataset and evaluated their mutation profiles. Ranking the mutations based on frequency we found an enrichment of mutations in NPM1, IDH2, IDH1, PML-RARA and FLT3-ITD in the low AHR expression group compared to the high expression group (Figure1A). AHR high patients had higher frequencies of CBF-MYH11, DNMT3A, FLT3 point mutations, NRAS, KRAS and BCOR mutations, compared to AHR low expressors.

To discuss, bilirubin, as a naturally occurring antiproliferative molecule, mediates growth inhibition by induction of cell cycle arrest and apoptosis in MCF-7 and MDA-MB-468 breast cancer cells. It is associated with the suppression of cyclin A, D1, and Bcl-2; induction of p53, p27, and Bax together with the activation of caspase-3 and - 9.

A luciferase reporter gene assay with the intronic region of TP63 showed that AHR expression increased reporter activity. Collectively, our findings suggest that HER2-activated AHR upregulates ΔNp63 expression and that this signaling cascade is involved in CSC maintenance in HER2-expressing breast cancers.

Radianspenes C and D, and dahliane D, bioactive compounds isolated from Nemania sp. EL006872 ELF, have the potential for use as immunotherapy and immunoncology treatments.

Clinically, the expression of circMET and AHR has enhanced in tamoxifen-resistant samples compared with tamoxifen sensitive samples, but miR-204-5p presented a revered expression in the samples. Consequently, we concluded that circular RNA circMET contributed to tamoxifen resistance of breast cancer cells by targeting miR-204-5p/AHR signaling.

Cav-1 overexpression enhanced sensitivity to cisplatin (CDDP) treatment, whereas Cav-1 deficiency promoted chemoresistance in OCCC cells...Of note, ACE2 positively regulated the expression of the platinum-clearing enzyme CYP3A4. These findings suggest that the Cav-1-ACE2 axis modulates xenobiotic metabolism-linked chemoresistance in OCCC, predicting potential roles for the stress sentinel networks in oncogenic processes.