Search

Background: Aspirin is a classic anti‐inflammatory drug and its anticancer effect has been previously explored in many types of cancer including colorectal cancer therapy. Programmed cell death‐ligand 1 (PD‐L1) is widely expressed in tumor cells and displays an inhibitory role in antitumor immunity. This study aimed to clarify the role of PD‐L1 in aspirin‐suppressed lung cancer. Methods: The inhibitory effect of aspirin on lung cancer cell proliferation was assessed using an MTT cell viability assay. The role of aspirin in the modulation of PD‐L1 expression was analyzed by western blot or RT‐PCR assays. In lung cancer cells, the influence of aspirin on PD‐L1 promoter activity was detected using a luciferase reporter assay. The interaction of TAZ with PD‐L1 promoter in the cells, with or without aspirin administration, was tested via chromatin immunoprecipitation (ChIP) analysis. The function of PD‐L1 in aspirin‐mediated growth inhibition of lung cancer was examined using a cell viability assay. Results: Following treatment with aspirin, lung cancer cell growth was markedly suppressed. Aspirin was able to markedly decrease the expression of PD‐L1 at the mRNA and protein levels in lung cancer cells. For the mechanism study, we found that the promoter of PD‐L1 was inactivated by aspirin via TAZ transcriptional coactivator in the cells. With regard to the functional investigation, aspirin was capable of resisting cell proliferation and PD‐L1 overexpression abolished aspirin‐depressed cell proliferation in lung cancer. Conclusions: Aspirin suppressed the growth of lung cancer cells via targeting the TAZ/PD‐L1 axis. [ABSTRACT FROM AUTHOR]

Transcription initiation has long been considered a primary regulatory step in gene expression. Recent work, however, shows that downstream events, such as transcription elongation, can also play important roles. 1–3 A well-characterized example from animals is promoter-proximal pausing, where transcriptionally engaged Pol II accumulates 30–50 bp downstream of the transcription start site (TSS) and is thought to enable rapid gene activation. 2 Plants do not make widespread use of promoter-proximal pausing; however, in a phenomenon known as 3′ pausing, a significant increase in Pol II is observed near the transcript end site (TES) of many genes. 4–6 Previous work has shown that 3′ pausing is promoted by the BORDER (BDR) family of negative transcription elongation factors. Here we show that BDR proteins play key roles in gene repression. Consistent with BDR proteins acting to slow or pause elongating Pol II, BDR-repressed genes are characterized by high levels of Pol II occupancy, yet low levels of mRNA. The BDR proteins physically interact with FPA, 7 one of approximately two dozen genes collectively referred to as the autonomous floral-promotion pathway, 8 which are necessary for the repression of the flowering time gene FLOWERING LOCUS C (FLC). 9–11 In early-flowering strains, FLC expression is repressed by repressive histone modifications, such as histone H3 lysine 27 trimethylation (H3K27me3), thereby allowing the plants to flower early. These results suggest that the repression of transcription elongation by BDR proteins may allow for the temporary pausing of transcription or facilitate the long-term repression of genes by repressive histone modifications. • BDR proteins repress expression of the floral repressor, FLC • BDR proteins physically interact with the autonomous pathway protein FPA • BDR-repressed genes have high levels of Pol II occupancy, despite low mRNA levels • Gene repression by BDR may involve the inhibition of transcription elongation Yu et al. show that genes repressed by the BDR family of negative transcription elongation factors have high levels of Pol II occupancy, despite relatively low steady-state RNA levels. In this way, BDR proteins may allow for the later resumption of transcription or facilitate the long-term repression of genes by repressive histone modifications. [ABSTRACT FROM AUTHOR]

The scavenger receptor class B, type I (SR-BI), is a member of the CD36 superfamily comprising transmembrane proteins involved in mammalian and fish lipid homeostasis regulation. We hypothesize that this receptor plays an important role in Macrobrachium nipponense lipid metabolism. However, little attention has been paid to SR-BI in commercial crustaceans. In the present study, we report a cDNA encoding M. nipponense scavenger receptor class B, type I (designated as MnSR-BI), obtained from a hepatopancreas cDNA library. The complete MnSR-BI coding sequence was 1545 bp, encoding 514 amino acid peptides. The MnSR-BI primary structure consisted of a CD36 domain that contained two transmembrane regions at the N- and C-terminals of the protein. SR-BI mRNA expression was specifically detected in muscle, gill, ovum, intestine, hepatopancreas, stomach, and ovary tissues. Furthermore, its expression in the hepatopancreas was regulated by dietary lipid sources, with prawns fed soybean and linseed oils exhibiting higher expression levels. RNAi-based SR-BI silencing resulted in the suppression of its expression in the hepatopancreas and variation in the expression of lipid metabolism-related genes. This is the first report of SR-BI in freshwater prawns and provides the basis for further studies on SR-BI in crustaceans. [ABSTRACT FROM AUTHOR]