MicroRNA-96-5p is negatively regulating GPC3 in the metastasis of papillary thyroid cancer.

Backgrounds: Papillary thyroid cancer is the most common pathological type of thyroid cancer. miR-96-5p, a member of the miR-183 family, constitute a polycistronic miRNA cluster. In breast cancer, miR-96-5p promotes cell invasion, migration, and proliferation in vitro by inhibiting PTPN9.

PGC1α: an emerging therapeutic target for chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN)-mediated paresthesias are a common complication in cancer patients undergoing chemotherapy. There are currently no treatments available to prevent or reverse CIPN. Therefore, new therapeutic targets are urgently needed to develop more effective analgesics.

Transcriptome Analysis Revealed Potential Neuro-Immune Interaction in Papillary Thyroid Carcinoma Tissues.

Background: A recent study reported that papillary thyroid carcinoma (PTC) was associated with increased adrenergic nerve density. Meanwhile, emerging evidence suggested that tumor-innervating nerves might play a role in shaping the tumor microenvironment. We aimed to explore the potential interaction between neuronal markers and tumor microenvironmental signatures through a transcriptomic approach.

Capn4 regulates Snail to promote the epithelial-mesenchymal transition of nasopharyngeal carcinoma by mediating the transcriptional activity of claudin-11.

The metastasis and recurrence of nasopharyngeal carcinoma (NPC) contribute to the poor prognosis of patients. Inhibiting epithelial-mesenchymal transition (EMT) is an effective strategy to obstruct metastasis. Therefore, this study aimed to explore the effects of Capn4 on the EMT of NPC cells and its specific mechanism of action.

Spatial colocalization and functional link of purinosomes with mitochondria.

Purine biosynthetic enzymes organize into dynamic cellular bodies called purinosomes. Little is known about the spatiotemporal control of these structures. Using super-resolution microscopy, we demonstrated that purinosomes colocalized with mitochondria, and these results were supported by isolation of purinosome enzymes with mitochondria.

Dynamic mass redistribution assay decodes differentiation of a neural progenitor stem cell.

Stem cells hold great potential in drug discovery and development. However, challenges remain to quantitatively measure the functions of stem cells and their differentiated products. Here, we applied fluorescent imaging, quantitative real-time PCR, and label-free dynamic mass redistribution (DMR) assays to characterize the differentiation process of the ReNcell VM human neural progenitor stem cell.

Thieno[3,2-b]thiophene-2-carboxylic acid derivatives as GPR35 agonists.

The optimization of a series of thieno[3,2-b]thiophene-2-carboxylic acid derivatives for agonist activity against the GPR35 is reported. Compounds were optimized to achieve β-arrestin-biased agonism for developing probe molecules that may be useful for elucidating the biology and physiology of GPR35. Compound 13 was identified to the most potent GPR35 agonist, and compounds 30 and 36 exhibited the highest efficacy to cause β-arrestin translocation.

Multiple tyrosine metabolites are GPR35 agonists.

Both kynurenic acid and 2-acyl lysophosphatidic acid have been postulated to be the endogenous agonists of GPR35. However, controversy remains whether alternative endogenous agonists exist. The molecular targets accounted for many nongenomic actions of thyroid hormones are mostly unknown.

Label-free phenotypic profiling identified D-luciferin as a GPR35 agonist.

Fluorescent and luminescent probes are essential to both in vitro molecular assays and in vivo imaging techniques, and have been extensively used to measure biological function. However, little is known about the biological activity, thus potential interferences with the assay results, of these probe molecules. Here we show that D-luciferin, one of the most widely used bioluminescence substrates, is a partial agonist for G protein-coupled receptor-35 (GPR35).

Discovery of Natural Phenols as G Protein-Coupled Receptor-35 (GPR35) Agonists.

We report the discovery and characterization of natural phenols as G protein-coupled receptor-35 (GPR35) agonists. Pharmacological characterization using label-free dynamic mass redistribution and Tango β-arrestin translocation assays revealed that GPR35-active natural phenols are divergent in their biased agonism.

Discovery of 2-(4-methylfuran-2(5H)-ylidene)malononitrile and thieno[3,2-b]thiophene-2-carboxylic acid derivatives as G protein-coupled receptor 35 (GPR35) agonists.

Screening with dynamic mass redistribution (DMR) assays in a native cell line HT-29 led to identification of two novel series of chemical compounds, 2-(4-methylfuran-2(5H)-ylidene)malononitrile and thieno[3,2-b]thiophene-2-carboxylic acid derivatives, as GPR35 agonists. Of these, 2-(3-cyano-5-(3,4-dichlorophenyl)-4,5-dimethylfuran-2(5H)-ylidene)malononitrile (YE120) and 6-bromo-3-methylthieno[3,2-b]thiophene-2-carboxylic acid (YE210) were found to be the two most potent GPR35 agonists with an EC(50) of 32.5 ± 1.

Tyrphostin analogs are GPR35 agonists.

GPR35 is an orphan G protein-coupled receptor that is not well-characterized. Here we employ dynamic mass redistribution (DMR) assays to discover new GPR35 agonists. DMR assays identified tyrphostin analogs as GPR35 agonists, which were confirmed with receptor internalization, Tango β-arrestin translocation, and extracellular-signal-regulated kinase phosphorylation assays.

Brain-specific factors in combination with mutant huntingtin induce gene-specific transcriptional dysregulation.

Mutant huntingtin lowered steady-state levels of DARPP-32 mRNA in the brain but not kidney of R6 transgenic HD mice by repressing transcription from one of two promoters. The activity of DARPP-32 promoter deletion constructs were lower in the presence of mutant huntingtin in immortalized striatal cell lines but no difference in transcription factor binding to the promoter was detected. The activity of CMV, TK and HPRT promoters was also affected by mutant huntingtin in these cell lines.

Mutant huntingtin affects the rate of transcription of striatum-specific isoforms of phosphodiesterase 10A.

Huntington's disease (HD) is caused by the inheritance of a copy of the gene encoding mutant huntingtin with an expanded CAG repeat. Phosphodiesterase 10A (PDE10A) mRNA decreases in transgenic HD mice expressing exon 1 of the human huntingtin gene (HD). The mouse PDE10A mRNA is expressed through alternative splicing and polyadenylation in a tissue-specific manner and that transcription of striatal PDE10A mRNA is driven by two promoters.

Structure, expression and regulation of the cannabinoid receptor gene (CB1) in Huntington's disease transgenic mice.

Loss of cannabinoid receptors (CB1) occurs prior to neurodegeneration in Huntington's disease (HD). The levels and distribution of CB1 RNA were equivalent in 3-week-old mice regardless of genotype demonstrating that the specific factors and appropriate chromatin structure that lead to the transcription of CB1 were present in the striatum of young R6/2 and R6/1 transgenic HD mice. The expression of the mutant HD transgene led progressively to decreased steady-state levels of CB1 mRNA in neurons of the lateral striatum, which was dependent on the size of the CAG repeat and relative expression of the gene encoding mutant huntingtin (HD).