MLPH (Melanophilin)

Our study depicts PAIM-specific proteomic characteristics and demonstrates the potential utility of new protein biomarkers for the differential diagnosis of PAIM and lmCRC. These findings may contribute to improving the diagnostic accuracy and guide appropriate treatments for these patients.

Both VOLph and CuLph showed remarkable interactive binding with ctDNA compared to the free ligand HLph, based on K = 16.31, 16.04 and 12.41 × 10 mol dm and ΔGb≠ = 47.11, -46.89, and -44.05 kJ mol for VOLph, CuLph, and HLph, respectively, due to the central metal ion (VO and Cu ions). VOLph (with a higher oxidation state of the V ion and oxo-ligand) exhibited enhanced interaction with the ctDNA molecule compared to CuLph, demonstrating the role and type of the central metal ion within the performed electronegative and electrophilic characters.

In addition, SGMFAb reduced the expressions of three melanosome-transport-participating proteins (myosin Va, melanophilin, and Rab27a) in α-MSH-stimulated B16BL6 cells. These results indicate that SGMFAb positively influences skin whitening activities by inhibiting melanogenesis and melanosome-transport-related events in B16BL6 cells, and suggest that SGMFAb is a promising material for developing functional skin whitening agents.

Our data demonstrate that MLPH exerts regulatory functions in GBM radiation resistance by promoting the NF-κB signaling pathway and that O-GlcNAcylation of MLPH both stabilizes and protects it from TRIM21-mediated ubiquitination. These results identify a potential mechanism of GBM radiation resistance and suggest a potential therapeutic strategy for GBM treatment.

In UVB-irradiated mouse ears, BJ-5ta-Ex reduced the number of active melanocytes and melanin granules. These results demonstrate that BJ-5ta-Ex can be useful for the clinical treatment of hyperpigmentation disorders.

These findings are currently being confirmed using Cancer Research Institute iAtlas, a database that contains gene expression for over 1,100 cancer patients across five different tissue types. Specific adjustments may be required to account for differences in gene expression measurements between the training and testing tests.

MLPH was positively associated with HOXA11-AS and overexpressed it accelerated the progression of prostate cancer. Taken together, HOXA11-AS elevated MLPH expression by sponging miR-148b-3p and accelerated prostate cancer cell proliferation.

Indirect CRISPR screening was established to isolate the responsible elements of cell-cell interactions. This screening method could reveal unknown mechanisms in all kinds of cell-cell interactions by revealing live phenotype-inducible cells, and it could be a platform for discovering new targets of drugs for conventional chemotherapies.

Abemaciclib not reported due to low numbers (n=16). We confirmed independent prognostic value of CES in first-line setting, suggesting a not statistically significant benefit with ribociclib vs palbociclib in CES-I. >

We show that reduced Ca -signaling after knockdown of ORAI1 gene also compromises the activity of melanophilin and Synaptotagmin-like protein 2, two proteins, which are important for correct localization of secretory organelles within cancer cells and their transport to sites of exocytosis. Thus, the Ca -channel ORAI1 and Ca -dependent proteins of the secretion pathway emerge as important targets for understanding and manipulating immune checkpoint blockade by PD-L1.

ER–/PgR+ BCs display a distinct mRNA expression profile characterized by the down-regulation of genes controlled by ESR1 and SUZ12. The latter as a part of Polycomb Repressive Complex 2 contributes to chromatin silencing, and some previous studies suggested its role in the regulation of steroid hormone receptors expression. Additionally, ER–/PgR+ BCs overexpress FOXC1 which is linked to more aggressive, high-grade, and treatment-resistant breast cancers.

And E2F1 may be involved in the process of drug resistance by regulating the MAPK signaling pathway. These might be useful as sensitive genes for the efficacy evaluation of neoadjuvant chemotherapy in breast cancer.

One patient with an AGAP3::BRAF fusion positive melanoma experienced a 30-month long response to trametinib. We show that, detecting fusions, especially in triple wild-type melanomas with TERT promoter mutations, may have a clinically significant impact in patients with advanced disease who have failed front-line immunotherapy.

These results indicated that Ro5-4864 induces melanogenesis in a TSPO-independent manner, which is inconsistent with previous research. This research is a reminder that we need to be very careful during target validation in drug development.

We found that rhamnazin inhibits intracellular transport of melanosomes through proteasomal degradation of MLPH. Our results suggest that topical application of rhamnazin may provide a new approach for treating skin pigmentation disorders.

The findings suggested that 5-demethylnobiletin may be considered as a potential natural product candidate for patients with pigment disorder.

HiChIP predicted enhancer elements at the AR and NKX3-1 prostate cancer risk loci, and both were experimentally confirmed to regulate expression of the corresponding genes through CRISPR interference (CRISPRi) perturbation in LNCaP cells. Our results demonstrate that looping data harbor additional information beyond eQTLs and expand the number of PrCa GWAS loci that can be linked to candidate susceptibility genes.

After uni- and multi-variable analysis of five-year survival, MLPH expression was still associated with lower DSS (hazard ratio (HR), 10.110; 95% confidence interval (CI), 2.178-46.920; p = 0.003) and MeFS (HR, 5.621; 95% CI, 1.762-17.931; p = 0.004). In conclusion, identifying MLPH expression could help to predict the response to chemoradiation and survival, and aid in personal therapeutic modification.

Variants within the melanophilin (MLPH) gene fell into this category. Depletion of MLPH in prostate organoid cultures, suggested a potential functional mechanism for impacting on cancer risk, as a serendipitous consequence of prior evolutionary benefits to another tissue.

Furthermore, salicylic acid treatment suppressed expression of transport complex-associated proteins melanophilin and myosin Va in two UVB-treated melanocytic cell lines, suppressed phagocytosis of fluorescent microspheres by UVB-stimulated human keratinocytes (HaCaT), inhibited protease-activated receptor 2 activation by reducing both Ca release and activation of phosphoinositide 3 kinase/AKT and mitogen-activated protein kinases and induced anti-melanogenic effects in zebrafish. Collectively, these results indicate that salicylic acid within ginseng root can inhibit melanocyte melanogenesis and melanin transport, while also suppressing keratinocyte phagocytic function.

 In BC PDXs, B-L biology associates with lower response to ribociclib monotherapy than Luminal or HER2-E. Ribociclib induces a luminal phenotype with high GE of estrogen-regulated genes and low GE of proliferation genes, a biological switch that could explain the better efficacy of ribociclib in the endocrine therapy (ET)-resistant HER2-E subtype observed in clinical trials when combined with ET.