MC1R (Melanocortin 1 Receptor)

Targeting MC1R could offer a novel strategy to enhance ferroptosis in CRC, potentially improving patient outcomes. This study elucidates the complex interactions between MC1R, Notch signaling, and ferroptosis, providing insights for developing targeted therapies in CRC.

These results demonstrate that isorhamnetin-3-O-neohespeidoside, a flavonoid glycoside from Typhae Pollen, acts through multiple mechanisms - direct enzyme inhibition, receptor downregulation, and autophagy induction - making it a promising natural candidate for hyperpigmentation treatment. Our integrated approach combining computational screening with experimental validation provides a robust framework for identifying multi-target depigmenting agents.

Both in vitro and in vivo experiments demonstrated that the melanocyte-targeted liposome formulation significantly outperformed pure glabridin and glabridin mixed with palmitoyl tripeptide-8 in terms of skin-whitening effects. Collectively, this study presents a promising liposome-based strategy for maximizing glabridin efficacy, offering a new potential avenue for melanoma treatment.

Here, we report that deficiency of DNA methylcytosine dioxygenase TET2 sensitizes HCC cells to sorafenib and verteporfin treatments. Notably, TET2-MC1R-YAP axis is evidenced in HCC specimens and plays a vital role in prognosis of HCC. Collectively, these findings not only elucidate a previously unidentified epigenetic regulatory mechanism of MC1R transcription and underscore the functional significance of MC1R signaling in tumorigenesis of HCC, but also provide potential targets and clinical strategies for HCC therapy.

Demographically, epidemiologically, and mechanistically, pigmentation status is central to CMM risk and a shared genetic susceptibility, comprising several pigmentation genes, between CMM and KCs. In the general population, CMM risk is associated with pale skin and poor tanning ability, mechanistically due to a relative lack of protection against UVR adduct formation, or perhaps via an alternate manner in individuals with abundant pheomelanin. Overall, evidence suggests that UVR exposure impacts CMM risk.

MC1R was a predictive factor for the prognosis of melanoma patients. Nomogram models based on MC1R demonstrated good prediction ability.

Self-assessed improved sun protection after diagnosis was significantly associated with reduced mortality due to melanoma. These results highlight the importance of improved sun awareness for patients after melanoma diagnosis, not only for preventing further melanomas but also reducing mortality risk.

A novel, likely pathogenic, missense variant (p.Y143C) in a medium penetrance melanoma-predisposing gene, melanocortin 1 receptor gene (MC1R), and two novel, likely pathogenic nonsense variants in low penetrance genes, p.Q218Ter in caspase 8 (CASP8) and p.Q40Ter in the fat mass- and obesity-associated (FTO) gene were detected. This study highlights the importance of elucidating the germline genetic background of melanoma, which may improve prediction of individual risk and the risk of family members and to optimize preventive, screening, and therapeutic measures for each patient and melanoma-prone families.

A significant reduction in nitric oxide was also observed in the B. alba-treated groups, along with a decrease in genes associated with pro-inflammatory cytokines, including IL-1β, IL-6, and COX-2. These findings suggest that B. alba has potential in the prevention of skin-related problems.

By regulating Tregs differentiation, MC1R overexpression in colon cancer correlates with poor prognosis, while MC1R inhibition shows potential as a therapeutic approach to slow tumor growth and enhance survival.

Our data suggest that MC1R might be a valuable drug target in aggressive melanoma. Additional studies are warranted to determine its functional significance in melanoma progression and its utility as a predictive biomarker in patients receiving MC1R-directed therapies.

Moreover, we found that NADPH oxidase (NOX)-dependent generation of ROS was responsible for AKT activation and oxidative DNA damage repair downstream of varMC1R. These observations provide a better understanding of the functional properties of melanoma-associated MC1R alleles and may be useful for the rational development of strategies to correct defective varMC1R responses for efficient photoprotection and melanoma prevention in fair-skinned individuals.