Borupsahin7772

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, is an aggressive cancer with a poor prognosis. Despite current management, the 5-year survival rate for patients with metastatic RMS is ∼30%; underscoring the need to develop better treatment strategies. We have recently reported that pannexin 1 (PANX1) levels are downregulated in RMS and that restoring its expression inhibits RMS progression. BI-2852 Here, we have surveyed and characterized the molecular changes induced by PANX1 re-expression in RMS. We cataloged transcriptomic changes in this context by RNA sequencing. At the protein level, we unveiled PANX1 interactors using BioID, complemented by co-immunoprecipitation coupled to high-performance liquid chromatography/electrospray ionization tandem mass spectrometry performed in PANX1-enriched fractions. Using these data, we generated searchable public databases for the PANX1 interactome and changes to the RMS transcriptome occurring when PANX1 expression is restored. STRING network analyses revealed a PANX1 interactome involving plasma membrane and cytoskeleton-associated proteins including the previously undescribed interactor AHNAK. Indeed, AHNAK knockdown abrogated the PANX1-mediated reduction in RMS cell viability and migration. Using these unbiased approaches, we bring insight to the mechanisms by which PANX1 inhibits RMS progression, identifying the cell migration protein AHNAK as a key modifier of PANX1-mediated changes in RMS malignant properties.The prognosis for patients with metastatic bladder cancer (BCa) is poor, and it is not improved by current treatments. RNA-binding motif protein X-linked (RBMX) are involved in the regulation of the malignant progression of various tumors. However, the role of RBMX in BCa tumorigenicity and progression remains unclear. In this study, we found that RBMX was significantly downregulated in BCa tissues, especially in muscle-invasive BCa tissues. RBMX expression was negatively correlated with tumor stage, histological grade and poor patient prognosis. Functional assays demonstrated that RBMX inhibited BCa cell proliferation, colony formation, migration, and invasion in vitro and suppressed tumor growth and metastasis in vivo. Mechanistic investigations revealed that hnRNP A1 was an RBMX-binding protein. RBMX competitively inhibited the combination of the RGG motif in hnRNP A1 and the sequences flanking PKM exon 9, leading to the formation of lower PKM2 and higher PKM1 levels, which attenuated the tumorigenicity and progression of BCa. Moreover, RBMX inhibited aerobic glycolysis through hnRNP A1-dependent PKM alternative splicing and counteracted the PKM2 overexpression-induced aggressive phenotype of the BCa cells. In conclusion, our findings indicate that RBMX suppresses BCa tumorigenicity and progression via an hnRNP A1-mediated PKM alternative splicing mechanism. RBMX may serve as a novel prognostic biomarker for clinical intervention in BCa.Fatty acid metabolism is essential for the biogenesis of cellular components and ATP production to sustain proliferation of cancer cells. Long-chain fatty acyl-CoA synthetases (ACSLs), a group of rate-limiting enzymes in fatty acid metabolism, catalyze the bioconversion of exogenous or de novo synthesized fatty acids to their corresponding fatty acyl-CoAs. In this study, systematical analysis of ACSLs levels and the amount of fatty acyl-CoAs illustrated that ACSL1 were significantly associated with the levels of a broad spectrum of fatty acyl-CoAs, and were elevated in human prostate tumors. ACSL1 increased the biosynthesis of fatty acyl-CoAs including C160-, C180-, C181-, and C182-CoA, triglycerides and lipid accumulation in cancer cells. Mechanistically, ACSL1 modulated mitochondrial respiration, β-oxidation, and ATP production through regulation of CPT1 activity. Knockdown of ACSL1 inhibited the cell cycle, and suppressed the proliferation and migration of prostate cancer cells in vitro, and growth of prostate xenograft tumors in vivo. Our study implicates ACSL1 as playing an important role in prostate tumor progression, and provides a therapeutic strategy of targeting fatty acid metabolism for the treatment of prostate cancer.Cutaneous melanoma tumors are heterogeneous and show diverse responses to treatment. Identification of robust molecular biomarkers for classifying melanoma tumors into clinically distinct and homogenous subtypes is crucial for improving the diagnosis and treatment of the disease. In this study, we present a classification of melanoma tumors into four subtypes with different survival profiles based on three distinct gene expression signatures keratin, immune, and melanogenesis. The melanogenesis expression pattern includes several genes that are characteristic of the melanosome organelle and correlates with worse survival, suggesting the involvement of melanosomes in melanoma aggression. We experimentally validated the secretion of melanosomes into surrounding tissues by melanoma tumors, which potentially affects the lethality of metastasis. We propose a simple molecular decision tree classifier for predicting a tumor's subtype based on representative genes from the three identified signatures. Key predictor genes were experimentally validated on melanoma samples taken from patients with varying survival outcomes. Our three-pattern approach for classifying melanoma tumors can contribute to advancing the understanding of melanoma variability and promote accurate diagnosis, prognostication, and treatment.DNA methylation plays a pivotal role in regulating cellular processes, and altered DNA methylation pattern is a general hallmark of cancer. However, DNA methylome in circulating tumor cells (CTCs) is still a mystery due to the lack of proper analytical techniques. We introduced an efficient workflow, LCM-µWGBS, which can efficiently profile the DNA methylation of microdissected CTC samples. LCM-µWGBS combines the laser capture microdissection (LCM)-based CTC capture method and whole-genome bisulfite sequencing in very small CTC population (µWGBS) to gain insight into the DNA methylation landscape of CTCs. We herein profiled the DNA methylome of CTCs from lung cancer patients. Deriving from a comprehensive analysis of CTC methylome, a unique "CTC DNA methylation signature" that is distinct from primary lung cancer tissues was identified. Further analysis showed that promoter hypermethylation of epithelial genes is a hallmark of stable epithelial-mesenchymal transition process. Moreover, it has been suggested that CTCs are endowed with a stemness-related feature during dissemination and metastasis. This work constitutes a unique DNA methylation analysis of CTCs at single base-pair resolution, which might facilitate to propose noninvasive CTC DNA methylation biomarkers contributing to clinical diagnosis.Aneuploidy is a hallmark of genomic instability that leads to tumor initiation, progression, and metastasis. CDC20, Bub1, and Bub3 form the mitosis checkpoint complex (MCC) that binds the anaphase-promoting complex or cyclosome (APC/C), a crucial factor of the spindle assembly checkpoint (SAC), to ensure the bi-directional attachment and proper segregation of all sister chromosomes. However, just how MCC is regulated to ensure normal mitosis during cellular division remains unclear. In the present study, we demonstrated that LNC CRYBG3, an ionizing radiation-inducible long noncoding RNA, directly binds with Bub3 and interrupts its interaction with CDC20 to result in aneuploidy. The 261-317 (S3) residual of the LNC CRYBG3 sequence is critical for its interaction with Bub3 protein. Overexpression of LNC CRYBG3 leads to aneuploidy and promotes tumorigenesis and metastasis of lung cancer cells, implying that LNC CRYBG3 is a novel oncogene. These findings provide a novel mechanistic basis for the pathogenesis of NSCLC after exposure to ionizing radiation as well as a potential target for the diagnosis, treatment, and prognosis of an often fatal disease.Determination of plasma aldosterone concentrations (PAC) and plasma active renin concentrations (ARC) is essential for the diagnosis of primary aldosteronism (PA). In Japan, although PAC and ARC are measured by radioimmunoassay and immunoradiometric assay, respectively, non-radioisotopic methods with better detection sensitivity, measurement accuracy, and technical simplicity are needed. We developed two-site sandwich chemiluminescent enzyme immunoassays (CLEIAs) to measure both PAC and ARC using monoclonal antibodies immobilized onto ferrite particles. The results of both assays are obtained simultaneously from a single plasma sample within 30 min using a fully automated system. The novel CLEIAs were validated using plasma samples from patients with PA (n = 52) and essential hypertension (n = 23). The PAC determined by the CLEIA was significantly correlated with that measured by liquid chromatography/mass spectrometry or conventional radioimmunoassay. The ARC determined by the CLEIA was significantly correlated with that measured by immunoradiometric assay. The limits of detection of the CLEIAs for PAC and ARC were 0.1 ng/dl and 0.04 pg/ml, respectively, which were better than those of conventional methods (PAC 2.5 ng/dl; ARC 5 pg/ml). link2 The PAC and PAC/ARC ratio (ARR) were significantly higher, and the ARC significantly lower, in patients with PA than in those with essential hypertension. An ARR cut-off of 1.31 ng/dl per pg/ml showed a sensitivity of 96.2% and specificity of 78.3% for PA screening. The newly developed CLEIAs for measuring PAC and ARC could provide a clinically powerful alternative to conventional methods used for hypertension screening in clinical practice.The project of identifying the cognitive mechanisms or information-processing functions that cause people to categorize others by their race is one of the longest-standing and socially-impactful scientific issues in all of the behavioral sciences. This paper addresses a critical issue with one of the few hypotheses in this area that has thus far been successful-the alliance hypothesis of race-which had predicted a set of experimental circumstances that appeared to selectively target and modify people's implicit categorization of others by their race. Here, we will show why the evidence put forward in favor of this hypothesis was not in fact evidence in support of the hypothesis, contrary to common understanding. We will then provide the necessary and crucial tests of the hypothesis in the context of conflictual alliances, determining if the predictions of the alliance hypothesis of racial categorization in fact hold up to experimental scrutiny. link3 When adequately tested, we find that indeed categorization by race is selectively reduced when crossed with membership in antagonistic alliances-the very pattern predicted by the alliance hypothesis. This finding provides direct experimental evidence that the human mind treats race as proxy for alliance membership, implying that racial categorization does not reflect attention to physical features per se, but rather to social relationships.Photonic curing has shown great promise in maintaining the integrity of flexible thin polymer substrates without structural degradation due to shrinkage, charring or decomposition during the sintering of printed functional ink films in milliseconds at high temperatures. In this paper, single-step photonic curing of screen-printed nickel (Ni) electrodes is reported for sensor, interconnector and printed electronics applications. Solid bleached sulphate paperboard (SBS) and polyethylene terephthalate polymer (PET) substrates are employed to investigate the electrical performance, ink transfer and ink spreading that directly affect the fabrication of homogeneous ink films. Ni flake ink is selected, particularly since its effects on sintering and rheology have not yet been examined. The viscosity of Ni flake ink yields shear-thinning behavior that is distinct from that of screen printing. The porous SBS substrate is allowed approximately 20% less ink usage. With one-step photonic curing, the electrodes on SBS and PET exhibited electrical performances of a minimum of 4 Ω/sq and 16 Ω/sq, respectively, at a pulse length of 1.