Retinoic acid receptor gamma is required for proliferation of pancreatic cancer cells.

Despite the expectation that retinoic acid receptor could be the potential therapeutic targets for pancreatic cancers, there has been the lack of information about the role and the impact of retinoic acid receptor gamma (RARγ, RARG) on pancreatic cancer, unlike other two RARs. Herein, we applied TCGA and GEO database to show that the expression and prognosis of RARG is closely related to pancreatic cancer, which demonstrates that RARG is commonly overexpressed in human pancreatic cancer and is an independent diagnostic marker predicting the poor prognosis of pancreatic cancer patients. In addition, we demonstrated that the reduction in the expression of RARG in human pancreatic cancer cells dramatically suppress their proliferation and tumor growth in vivo, partially attributable to the downregulation of tumor-supporting biological processes such as cell proliferation, antiapoptosis and metabolism and the decreased expression of various oncogenes like MYC and STAT3. Mechanistically, RARG binds on the promoters of MYC, STAT3, and SLC2A1 which is distinguished from well-known conventional Retinotic acid response elements (RAREs) and that the binding is likely to be responsible for the epigenetic activation in the level of chromatin, assessed by the measurement of deposition of the gene activation marker histone H3 K27 acetylation (H3K27ac) using ChIP-qPCR. In this study, we reveal that RARG plays important role in the tumorigenesis of pancreatic cancer and represents new therapeutic targets for human pancreatic cancer.

Citrus Flavone Tangeretin Inhibits CRPC Cell Proliferation by Regulating Cx26, AKT, and AR Signaling.

Prostate cancer (PCa) progression depends on the action of androgen receptors (AR). Therefore, preventing ligand-mediated activation of AR is the first-line treatment strategy for metastatic PCa. Androgen deprivation therapy (ADT) can inhibit ligand binding to AR and alleviate PCa progression initially. However, due to the adaptation of PCa and recovery of AR signaling, castration-resistant prostate cancer (CRPC) eventually develops. Exploring novel dietary compounds that can target AR signaling appears to be a viable alternative therapeutic option for CRPC. In the present study, compounds from the citrus fruits were focused upon, which contain various flavonoid ingredients. Key components contained within orange peel, which is frequently used in traditional Chinese medicine, and downstream targets were first analyzed using network pharmacology approach. Notably, it was found that tangeretin, an active ingredient from orange peel, can significantly inhibit CRPC cell (C4-2 and Du145 cells) proliferation and migration whilst also synergistically increasing the sensitivity of CRPC cells to anti-tumor drugs sorafenib or cisplatin. Tangeretin also significantly reduced AR and AKT expressions in C4-2 cells and signal transducer and activator of transcription 3 expression in the androgen-insensitive cell line Du145. In addition, tangeretin increased the expression of both connexin26 (Cx26) and gap junction function, which may mediate the bystander effects of cisplatin or sorafenib. Taken together, the present study revealed a novel molecular mechanism by which tangeretin may inhibit the proliferation of CRPC cells, by affecting the Cx26/AKT/AR pathway, to synergistically increase the sensitivity of CRPC cells to sorafenib and cisplatin.

Selection of candidate genes affecting meat quality and preliminary exploration of related molecular mechanisms in the Mashen pig.

OBJECTIVE: The aim of this study was to select the candidate genes affecting meat quality and preliminarily explore the related molecular mechanisms in the Mashen pig. METHODS: The present study explored genetic factors affecting meat quality in the Mashen pig using RNA sequencing (RNA-Seq). We sequenced the transcriptomes of 180-day-old Mashen and Large White pigs using longissimus dorsi to select differentially expressed genes (DEGs). RESULTS: The results indicated that a total of 425 genes were differentially expressed between Mashen and Large White pigs. A gene ontology enrichment analysis revealed that DEGs were mainly enriched for biological processes associated with metabolism and muscle development, while a Kyoto encyclopedia of genes and genomes analysis showed that DEGs mainly participated in signaling pathways associated with amino acid metabolism, fatty acid metabolism, and skeletal muscle differentiation. A MCODE analysis of the protein-protein interaction network indicated that the four identified subsets of genes were mainly associated with translational initiation, skeletal muscle differentiation, amino acid metabolism, and oxidative phosphorylation pathways. CONCLUSION: Based on the analysis results, we selected glutamic-oxaloacetic transaminase 1, malate dehydrogenase 1, pyruvate dehydrogenase 1, pyruvate dehydrogenase kinase 4, and activator protein-1 as candidate genes affecting meat quality in pigs. A discussion of the related molecular mechanisms is provided to offer a theoretical basis for future studies on the improvement of meat quality in pigs.