LPAR6 (Lysophosphatidic Acid Receptor 6)

Notably, silencing P2RY1 alleviated melanoma cells progression by TRIM63 depletion. Collectively, these data suggested that TRIM63 contributed to melanoma cells growth and mobility by ubiquitination of P2RY1 and may be a promising candidate as a potential diagnostic and therapeutic marker for patients with melanoma.

Further drug virtual screening identified Dutasteride as a potential inhibitor of LPAR6. AGPAT3 is an important gene related to the prognosis of osteosarcoma. Its ability to modulate LPA signaling and TAM activity offers promising therapeutic opportunities for improving osteosarcoma treatment, particularly in immunotherapy contexts.

Hypoxia upregulates lipid storage-related genes and accumulation of lipid droplets, which can be reversed upon restoration of histone H3 lysine 27 acetylation (H3K27ac) with a histone deacetylase inhibitor. We emphasize the importance of hypoxic stress as a strong intratumoral and epigenomic regulator of myeloid cell functions, which adds a new dimension to the characterization of particular GAM subpopulations.

Both showed beneficial effects, while overexpression of P2Y2 promotes cisplatin-induced cell death. Taken together, our study, for the first time revealed that P2Y2 plays an important role in CIA by regulating oxidative stress, inflammation, apoptosis, and necroptosis and its inhibitor, AR-C, is a potential drug for treating CIA.

The transcriptional data were confirmed demonstrating an UTP-promoted reduction in the number of γH2AX+ positive cells in etoposide-treated fibrotic primary hepatocytes...This regulation was also investigated pharmacologically by activating or blocking the signaling from either P2Y2 receptor or HIF-1α. Our work, in summary, shows a novel relationship between P2Y2 receptor-dependent purinergic signaling and DNA-dr-dbs in hepatic fibrosis.

Transcriptomic analysis combined with Western blot experiments demonstrated that LPA/LPAR6 inhibits YAP/TAZ nuclear translocation, thereby suppressing HCC cell proliferation and migration. In conclusion, these findings suggest that enhancing LPAR6 expression or developing LPAR6 agonists may offer a promising therapeutic strategy for adjuvant cancer treatment.

We further uncover the mechanisms of LPAR6 activation and principles of G-protein coupling. The structural information revealed by our study lays the groundwork for understanding LPAR6 signaling and provides a rational basis for designing compounds targeting LPAR6.

Single-cell transcriptomics from human choroidal datasets show the expression of P2RY1, but not other ADP receptors, in EC with a pattern similar to VEGFR2. Although ADP has been reported to be a growth inhibitor for vascular EC, here we describe its growth-stimulating effects for BCEC and other eye-derived EC.

In summary, we present a prognostic model intricately linked with immune status and treatment response. For ccRCC patients undergoing immunotherapy, this approach holds promise in aiding clinical decision-making by providing more precise and tailored treatment recommendations.

LPAR2 and PLPP2 inhibition are also predicted to have potential therapeutic utility. Future multi-omics investigations are necessarily to validate which LPA signaling components are high-value candidates for pharmacological manipulation in PDAC treatment.

Identifying biomarkers based on the expression levels of CD8+ T cell-related genes may be an effective approach for establishing prognostic models in AM patients. The independently prognostic risk evaluation model we constructed provides new insights and theoretical support for immunotherapy in AM.

We report the oldest patient diagnosed with 46, XY DSD. There have not yet been any reports of familial 46, XY DSD with a concurrent diagnosis of Ph+BCR::ABL1P210+ ALL with a rarely reported RCBTB2::LPAR6 fusion gene.