SULT1E1 (Sulfotransferase Family 1E Member 1)

Based on analyses of public databases and computational predictions, DHA may exert anti-HCC effects by regulating the p53 signaling pathway, cell cycle progression, and the LMRGs. However, these potential regulatory mechanisms require further experimental validation to confirm their biological relevance.

SIGNIFICANCE STATEMENT: This study investigated compensatory or coordinated changes in gene expression of drug-metabolizing enzymes and transporters in multidrug resistance-associated protein (MRP) 2-knockdown HepG2 cells and in the liver of MRP2-deficient rats. Decreased expression of MRP2 affects the gene expression of drug-metabolizing enzymes and transporters, including a decrease in SULT1E1, likely through nuclear receptor activation by endogenous molecules.

A causal association was observed between reduced sleep duration and an elevated risk of SCC. Mediation analysis demonstrated that SULT1E1 mediated 9.3% of the total effect of reduced sleep duration on SCC development.

Brain microdialysis further confirmed this discrepancy. These findings provide a foundation for exploring the pharmacological roles of CAP and its sulfated metabolites, particularly within the central nervous system.

With HN-375 in hand, a practical fluorescence-based assay was established for high-throughput screening and characterization of hSULT1E1 inhibitors, as such two potent hSULT1E1 inhibitors were identified from in-house compound libraries. Collectively, this study showcases a groundbreaking strategy for engineering highly specific and sensitive fluorogenic substrates for target conjugative enzyme(s), while HN-375 emerges as a practical tool for sensing SULT1E1 activity in a biological context and for the high-throughput screening of inhibitors.

Overall, our findings highlight the potential of DADS and DATS as promising agents for preventing and treating breast cancer by decreasing STS protein expression and suppressing active estrogen levels in breast cancer cells.

Notably, our study showed that proteomes sampled with e-biopsy from cSCC and BCC lesions are different and that proteins of CRNN, SULT1E1, and ITPK1 genes are significantly overexpressed in BCC in comparison with those in cSCC. Our results provide evidence that the e-biopsy approach could potentially be used as a tool to support cutaneous lesions classification with molecular pathology.

Breast cancers associate with SULT1E1, HIF1α and MMPs deregulations. For the first time, we are revealing that advanced cancer tissue with elevated SULT1E1-protein may reactivate in a reducing-state initiated by chalcone, but remain dormant in an oxidative environment. Furthermore, increased SULT1E1 protein synthesis is caused by DAS-induced mRNA expression. The combined effects of the drugs might decrease MMPs and HIF1α expressions. Further studies are necessary.

Notably, the cancer inhibition efficacy of NCG was superior to that of both NAR and the positive control tamoxifen, and was accompanied by increased hepatic EST expression and reduced estradiol levels in the liver, blood, and tumor tissue. Moreover, few side effects were observed after NCG treatment. Our findings reveal NCG as a promising candidate for endocrine therapy and highlight hepatic EST targeting as a novel therapeutic strategy for HR+ breast cancer.

In addition, SULT2A1 knockdown HCC cells promoted the proliferation and activation of hepatic stellate cells (HSCs), thereby exerting a potential stroma remodeling effect. Our study revealed the expression and role of SULTs genes in HCC and identified the contribution of SULT2A1 to the initiation and progression of HCC.

Molecular modeling and dynamics studies showed that the ligand prefers stacking over the 5'-quartet of c-MYC G4 using the aromatic ring of the ligand. Overall, the findings of this study demonstrate that even G4 ligands can accommodate nonplanar scaffolds, which opens up new avenues for ligand design.