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Adult Ocular and Orbital (Ocular Adnexa) Tumors
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
P.N. Plowman, Rachel Lewis, J.L. Hungerford
It has long been recognized that cytogenetics can be prognostic in uveal melanoma, and loss of chromosome 3 (monosomy 3) is associated with poor prognosis. More recently, it has been realized that the biology of uveal melanoma differs from that of cutaneous melanoma. The vast majority (85–95%) of uveal melanoma is characterized by activating mutations in genes encoding the G-protein-alpha subunits GNAQ or GNA11, which lead to stimulation of the MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt pathways,13–15 as well as the transcriptional co-activator Yes-associated protein 1 (YAP1) through the Trio-Rho/Rac signaling circuit. Additional mutations mutually exclusive to those in GNAQ/11 have been identified in phospholipase C β4 (PLCB4) and the G-protein coupled receptor cysteinyl leukotriene receptor 2 (CYSLTR2), affirming the importance of the G-alpha signaling pathway in uveal melanoma.
Effect of feeding regimen on circadian activity rhythms of food anticipatory by ghrelin hormone in a pig model
Published in Nutritional Neuroscience, 2023
He Zhang, Xiaoxi Yan, Ailian Lin, Pengke Xia, Menglan Jia, Yong Su
To determine the factors most likely to affect the circadian system, differential expression gene profiles of the hypothalamus (Fold Change > 1.5 or < 0.67; P < .05) were selected to overlay the circadian entrainment pathway. Table 2 revealed that the PLCB4 gene was strongly inhibited in M3 and M5 groups compared with M1 group. Quantitative analysis also confirmed that the relative expression levels of the PLCB4 and CAMKII genes in M1 group were higher than those in M3 and M5 groups (P < .05) (Figure 8(B)). Moreover, the GHS-R1a protein level in the hypothalamus tissue of pigs in the M1 group was significantly higher than that in M3 and M5 groups (P < .05) (Figure 8(A)). Compared with the P1 group, the lower PLCB4 and CAMKII genes mRNA levels in hypothalamus tissue of the D1 group (P < .05) (Figure 8(D, E)), indicating that ghrelin could regulate the expression of PLCB4 and CAMKII genes. Moreover, the relative expression of major clock genes in hypothalamus tissue was significantly affected (Figure 8(C, F)).
Hyperthermia promotes exosome secretion by regulating Rab7b while increasing drug sensitivity in adriamycin-resistant breast cancer
Published in International Journal of Hyperthermia, 2022
Di Xu, Wen-Juan Tang, Yi-Zhi Zhu, Zhen Liu, Kai Yang, Ming-Xing Liang, Xiu Chen, Yang Wu, Jin-Hai Tang, Wei Zhang
To explore the molecular mechanisms underlying this thermal regulation in breast cancer, we analyzed the genome-wide gene expression profiles of hyperthermia-treated MCF-7/ADR cells. Using microarray analysis, we identified 2046 upregulated genes and 1724 downregulated genes with the following criteria: (i) p value <.05, (ii) q value <.05, and (iii) fold change >2 (Figure 3(A, B)). The top 20 DEGs after hyperthermia treatment in MCF7/ADR cells are listed in Supplement Tables 2 and 3. Furthermore, to explore the hub genes that play important roles in the molecular mechanisms of hyperthermia treatment, we constructed a PPI network using Cytoscape (Figure 3(C)). This PPI network included an interaction network and functional nodes which indicated the biological response of MCF7/ADR cells to hyperthermia. From the PPI network, we analyzed 300 nodes (203 upregulated genes and 97 downregulated genes) and found 673 interaction pairs. Furthermore, a total of 10 genes were identified as hub genes with ≥8 degrees, as shown in Table 1. From the 10 hub genes, we found that MAPK8, NFKB1, PLCB4, FOS, CREB5, and RAC2 were significantly related to OS. With the higher expression of MAPK8, NFKB1, FOS, CREB5, and RAC2, the prognosis of patients is better. With the lower expression of PLCB4, the prognosis of patients was better (Figure 3(D)). The upregulation and downregulation of these genes resulted from hyperthermia treatment-induced prognostic changes, which is consistent with how hyperthermia can improve the prognosis of breast cancer.
Bioinformatics analysis of GNAQ, GNA11, BAP1, SF3B1,SRSF2, EIF1AX, PLCB4, and CYSLTR2 genes and their role in the pathogenesis of Uveal Melanoma
Published in Ophthalmic Genetics, 2021
PLCB4 (p.D630) and CYSLTR2 (p.L129) mutations cause activation of proteins and increased stimulation of the common signaling pathway. PLCB4 is a key player in intracellular signaling, acting downstream of GNAQ and GNA11 (1,5,40,41). PLCB4 is also known to indirectly activate the AKT/mTOR pathway via the mitogen-activated protein kinase (MAPK) and the downstream effector RasGRP3 (1,5,42,43). As we know, MAPK and AKT/mTOR promote cell growth and proliferation and are usually overexpressed in cancer (42,43). PLCB4 D630 missense mutation is known to be a driver mutation. It has been reported that the p.L129Q CYSLT2R mutant protein structurally activates endogenous Gaq, is oncogenic in UM patients, and has a critical role in UM pathogenesis by uncontrolled activation of Gaq signaling (42–45). This mutation was found in three patients (2.8%), which were both GNAQ and GNA11 wild-type, the CYSLTR2 p.L129Q missense mutation is likely to be the initiating oncogenic event. Nell et al. (46) published a similar analysis on a comparable UM cohort and correlated the p.L129Q missense mutation with an increased CYSLTR2 m-RNA expreesion level.