This study aimed to explore the influence of Tryptophanyl-tRNA synthetase (WARS) expression on the proliferation and migration of uveal melanoma (UM) cells, and the potential mechanisms.
This study aimed to explore the influence of Tryptophanyl-tRNA synthetase (WARS) expression on the proliferation and migration of uveal melanoma (UM) cells, and the potential mechanisms.
Uveal melanoma (UM) remains without effective therapy at the metastatic stage, which is associated with <i>BAP-1</i> (BRCA1 associated protein) mutations.
Activation of NFκB1/p50 was evaluated in 75 cases of uveal melanoma by immunohistochemistry. mRNA expression in 58 fresh UM specimen was measured by quantitative reverse-transcriptase PCR (qRT-PCR).
We show that YAP/TAZ activation induced by Lats1/2 deletion cooperates with Kras to promote UM progression via downstream transcriptional reinforcement.
Finally, Mel202/DR1/CD80 uveal melanoma vaccine cells expressed the intercellular adhesion molecule 1 (ICAM-1) that was pivotal for CD4+ T cell activation via lymphocyte function-associated antigen 1(LFA-1).
We first performed an immunostaining with the alpha-smooth muscle actin (αSMA) to localize activated HSteCs in UM liver macro-metastases from four patients.
<b>Materials and methods:</b> We analyzed the expressions of SKP2 in different UM cell lines compared with normal pigment cell by RNA-seq, RT-qPCR and Western blot.
Interleukin 6, 8 (IL-6, IL-8, respectively), interferon-inducible protein-10 (IP-10), placental growth factor1 (PIGF1), regulated on activation, normal T Cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1), nerve growth factor-beta (NGF-β), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and vascular endothelia growth factor A (VEGF-A) were assessed by multiplex bead assay.In the study group, significantly higher concentrations of IL-6 (P = .006), IL-8 (P = .018), IP-10 (P = .004), RANTES (P = .008), MCP-1 (P = .02), NGF-β (P = .013), EGF (P < .001), PIGF1 (P = .01), bFGF (P = .016), and VEGF (P = .017) were measured, when compared with the control group.Several angiogenic, inflammatory, and chemotactic cytokines are highly expressed in the aqueous humor of the UM eyes, which provides new insights into the pathophysiology of UM and could be potential targets for treatment.
Uveal melanoma (UM) remains without effective therapy at the metastatic stage, which is associated with <i>BAP-1</i> (BRCA1 associated protein) mutations.
Our data highlight the functional significance of Lats-YAP/TAZ in UM initiation and progression in vivo and suggest combination inhibition of YAP/TAZ and Ras/MAPK as a new therapeutic strategy for UM.
Here, we evaluated the mechanisms of BETi resistance in uveal melanoma, a disease with little treatment options, using two approaches: a high-throughput combinatorial drug screen with the clinical BET inhibitor PLX51107 and RNA sequencing of BETi-resistant cells.