AHR expression

In breast cancer patients, the expression of AHR and PD-L1 was correlated with increased Treg cell infiltration, and higher levels of AHR were associated with a poor prognosis. These findings reveal that the crosstalk of breast cancer cells, lung macrophages, and Treg cells via the GM-CSF-STAT5-AHR-PD-L1 cascade modulates the lung pre-metastatic niche during breast cancer progression.

This study emphasizes the importance of developing targeted therapies that address the specific genetic and molecular profiles of different populations. By gaining a deeper understanding of the roles of AHR and AR signaling in prostate cancer, particularly in the context of ethnic diversity, we aim to work toward reducing these disparities and improving outcomes for all patients.

In addition, we showed that the effect of AHR overexpression on cisplatin-induced apoptosis could be rescued by either XIAP siRNA or miR-142-5p mimic. Thus, our findings reveal important insights into the molecular mechanism underlying the dysregulation of XIAP in ovarian cancer, indicating that AHR serves as the ceRNA that competes miR-142-5p with XIAP and subsequently affects the platinum-based chemotherapy.

Blocking AhR with CLF reduces AhR expression, inhibits Kyn-mediated proliferation of SCLC cells, and induces apoptosis and cell cycle arrest in the G2/M phase; further, our examination indicates that Kyn treatment also promotes osteoblast-mediated osteoclast differentiation through RANKL. The treatment with CLF impedes RANKL expression and osteoclastogenesis, suggesting that CLF has the potential for developing SCLC therapies that have efficacies against bone metastasis.

Moreover, in breast cancer patients, the expression of AhR and its downstream genes may be closely associated with cancer progression in patients. Therefore, an increase in UA could promote the proliferation of breast cancer cells through the AhR/p27Kip1/cyclin E1 pathway axis.

The findings describe the metabolic landscape of HNSCC comprehensively and reveal that the Kyn/Siglec-15 axis may be a novel potential immunometabolism mechanism, providing a promising therapeutic strategy for cancers.

Interestingly, the expression patterns of AhR were categorized into three clusters based on the cancer type, with high AhR expression levels being found in regulatory T cells (Tregs) in non-small cell lung cancer (NSCLC). These findings are anticipated to serve as pivotal evidence for the design of clinical trials and the analysis of the anticancer mechanisms of AhR-targeting therapies.

The AhR pathway plays a crucial role in regulating immune responses within the respiratory and intestinal barriers when they are invaded by viruses, bacteria, parasites, and fungi. Additionally, we propose that targeting the agonist and antagonist of AhR signaling pathways could serve as a promising therapeutic approach for combating pathogen infections, especially in light of the growing prevalence of drug resistance to multiple antibiotics.

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.