Effect of miR-184 and miR-205 on the tumorigenesis of conjunctival mucosa associated lymphoid tissue lymphoma through regulating RasL10B and TNFAIP8

AIM: To explore the effect of miR-184 and miR-205 on the proliferation and metastasis of conjunctival mucosa associated lymphoid tissue (MALT) lymphoma. METHODS: Tissue of tumor and adjacent normal control from 5 patients with conjunctival MALT was included. RPMI8226 cell line was selected to verify the effect of miRNAs in B cells. The function of microRNA on the RPMI8226 cell apoptosis, migration and invasion was evaluated by apoptosis assay and Transwell assay. The mRNA and protein expression were examined by quantitative RT-PCR and Western blotting. The effect of microRNA on regulation of downstream gene expression was evaluated by luciferase report assay. RESULTS: A decreased level of miR-184 and miR-205 was observed in MALT lymphoma tissue. Exogenous miR-184 and miR-205 analogues promoted apoptosis, and inhibited the survival, migration, and invasion of RPMI8226 cells. miR-184 and miR-205 inhibitor reversed the process. The RNA and protein level of RasL10B and TNFAIP8 were downregulated in MALT lymphoma tissue. The exogenous of miR-184 and miR-205 promoted the expression of RasL10B and TNFAIP8. Meanwhile, inhibition of miR-184 and miR-205 repressed the expression of target gene, RasL10B and TNFAIP8. CONCLUSION: miR-184 and miR-205 suppresses the tumorigenesis of conjunctival MALT lymphoma through regulating RasL10B and TNFAIP8.

Methionine Metabolism in Aging Regulation

Aging is the major risk factor for many diseases but the mechanisms are poorly understood. The risk of developing hepatic steatosis increases with age and the health impact of this disease is negative and high. When challenged with high fat diets, long living Ames mice withstand the detrimental metabolic effects that occur in normal mice. We examined transcriptomic and epigenomic profiles of Ames and wild type hepatocytes in the presence or absence of fat to demonstrate that the epigenomic profile drives transcription factor and downstream gene expression resulting in susceptibility or resistance to fatty liver disease. We found that markers of steatosis are related to gene expression in wild type and Ames mice, and dwarf mice retain fewer lipid droplets compared to wild type mice. These studies will provide data to guide our understanding of mechanisms leading to hepatic disease and define factors that provide protection from age-related metabolic disorders.

Roles of plant hormones in thermomorphogenesis

Global warming has great impacts on plant growth and development, as well as ecological distribution. Plants constantly perceive environmental temperatures and adjust their growth and development programs accordingly to cope with the environment under non-lethal warm temperature conditions. Plant hormones are endogenous bioactive chemicals that play central roles in plant growth, developmental, and responses to biotic and abiotic stresses. In this review, we summarize the important roles of plant hormones, including auxin, brassinosteroids (BRs), Gibberellins (GAs), ethylene (ET), and jasmonates (JAs), in regulating plant growth under warm temperature conditions. This provides a picture on how plants sense and transduce the warm temperature signals to regulate downstream gene expression for controlling plant growth under warm temperature conditions via hormone biosynthesis and signaling pathways.

Bidirectional regulation of calcium release–activated calcium (CRAC) channel by SARAF

Store-operated calcium entry (SOCE) through the Ca2+ release–activated Ca2+ (CRAC) channel is a central mechanism by which cells generate Ca2+ signals and mediate Ca2+-dependent gene expression. The molecular basis for CRAC channel regulation by the SOCE-associated regulatory factor (SARAF) remained insufficiently understood. Here we found that following ER Ca2+ depletion, SARAF facilitates a conformational change in the ER Ca2+ sensor STIM1 that relieves an activation constraint enforced by the STIM1 inactivation domain (ID; aa 475–483) and promotes initial activation of STIM1, its translocation to ER–plasma membrane junctions, and coupling to Orai1 channels. Following intracellular Ca2+ rise, cooperation between SARAF and the STIM1 ID controls CRAC channel slow Ca2+-dependent inactivation. We further show that in T lymphocytes, SARAF is required for proper T cell receptor evoked transcription. Taking all these data together, we uncover a dual regulatory role for SARAF during both activation and inactivation of CRAC channels and show that SARAF fine-tunes intracellular Ca2+ responses and downstream gene expression in cells.

Transcriptional signatures of cell-cell interactions are dependent on cellular context

Cell-cell interactions are often predicted from single-cell transcriptomics data based on observing receptor and corresponding ligand transcripts in cells. These predictions could theoretically be improved by inspecting the transcriptome of the receptor cell for evidence of gene expression changes in response to the ligand. It is commonly expected that a given receptor, in response to ligand activation, will have a characteristic downstream gene expression signature. However, this assumption has not been well tested. We used ligand perturbation data from both the high-throughput Connectivity Map resource and published transcriptomic assays of cell lines and purified cell populations to determine whether ligand signals have unique and generalizable transcriptional signatures across biological conditions. Most of the receptors we analyzed did not have such characteristic gene expression signatures - instead these signatures were highly dependent on cell type. Cell context is thus important when considering transcriptomic evidence of ligand signaling, which makes it challenging to build generalizable ligand-receptor interaction signatures to improve cell-cell interaction predictions.

Role of LncRNA CASC9 in oral carcinoma and its downstream gene expression and mechanism detected by nanomagnetic bead-based polymerase chain reaction

In view of the increasing incidence of oral carcinoma (OC), an in-depth understanding of the mechanism is required for future prevention and treatment. In modern medical research, the etiology of tumor diseases is mainly focused on gene changes, among which lncRNA is a trending topic. We speculated that lncRNA CASC9 may attribute to OC occurrence. To verify our conjecture, we extracted the total RNA of the research samples through nanomagnetic beads, detected the expression of CASC9 downstream genes miR-383-5p and KIF3B by polymerase chain reaction (PCR), and analyzed the impact of the three on OC cells and the targeting relationship. The total RNA extracted by nanomagnetic beads were found to be able to effectively improve the PCR speed, yield and the accuracy of the results, and reduce the allergic amplification results of the samples to be tested to obtain the best results. The detection result showed high CASC9 and KIF3B expression, and low miR-383-5p expression in OC cells. Inhibition of CASC9 and KIF3B and elevation of miR-383-5p can inhibit the viability of OC cells and boost apoptosis. Through dual-luciferase reporter (DLR) assay, the targeted regulation relationship between CASC9 and miR-383-5p and between miR-383-5p and KIF3B, was determined. Rescue experiments confirmed that CASC9 was able to modulate OC cell biological behaviors by targeting the miR-383-5p/KIF3B axis. Therefore, we argue that with high expression in OC, CASC9 can enhance the proliferation and migration of OC cells and inhibit the apoptosis through targeting the miR-383-5p/KIF3B axis.

Metabolite Profiling of Pig Seminal Plasma Identifies Potential Biomarkers for Sperm Resilience to Liquid Preservation

Metabolomic approaches allow the study of downstream gene expression events since metabolites are considered as the products of cell signaling pathways. For this reason, many studies in humans have already been conducted to determine the influence of the metabolites present in seminal plasma (SP) on sperm physiology, and to identify putative biomarkers. However, in livestock species, these relationships are yet to be uncovered. Thus, the present study aimed to explore: (i) if concentrations of metabolites in pig SP are related to sperm quality and functionality, and (ii) if they could predict the sperm resilience to liquid storage at 17°C. To this end, 28 ejaculates were individually collected and split into three aliquots: one was used for SP analysis through nuclear magnetic resonance (NMR) spectroscopy; another served for the evaluation of sperm concentration and morphology; and the last one was utilized to determine sperm functionality parameters using computer-assisted sperm analysis (CASA) and flow cytometry after 0 h and 72 h of liquid-storage at 17°C. NMR analysis allowed the identification and quantification of 23 metabolites present in pig SP which, except for fumarate, were not observed to follow a breed-dependent behavior. Moreover, specific relationships between metabolites and sperm variables were identified: (i) glutamate, methanol, trimethylamine N-oxide, carnitine, and isoleucine were seen to be related to some sperm quality and functionality parameters evaluated immediately after semen collection; (ii) leucine, hypotaurine, carnitine and isoleucine were found to be associated to the sperm ability to withstand liquid storage; and (iii) Bayesian multiple regression models allowed the identification of metabolite patterns for specific sperm parameters at both 0 h and 72 h. The identification of these relationships opens up the possibility of further investigating these metabolites as potential sperm functional biomarkers.

Tumor Immune Microenvironment and Its Related miRNAs in Tumor Progression

MiRNA is a type of small non-coding RNA, by regulating downstream gene expression that affects the progression of multiple diseases, especially cancer. MiRNA can participate in the biological processes of tumor, including proliferation, invasion and escape, and exhibit tumor enhancement or inhibition. The tumor immune microenvironment contains numerous immune cells. These cells include lymphocytes with tumor suppressor effects such as CD8+ T cells and natural killer cells, as well as some tumor-promoting cells with immunosuppressive functions, such as regulatory T cells and myeloid-derived suppressor cells. MiRNA can affect the tumor immune microenvironment by regulating the function of immune cells, which in turn modulates the progression of tumor cells. Investigating the role of miRNA in regulating the tumor immune microenvironment will help elucidate the specific mechanisms of interaction between immune cells and tumor cells, and may facilitate the use of miRNA as a predictor of immune disorders in tumor progression. This review summarizes the multifarious roles of miRNA in tumor progression through regulation of the tumor immune microenvironment, and provides guidance for the development of miRNA drugs to treat tumors and for the use of miRNA as an auxiliary means in tumor immunotherapy.

Genetic perturbation of PU.1 binding and chromatin looping at neutrophil enhancers associates with autoimmune disease

Neutrophils play fundamental roles in innate immune response, shape adaptive immunity, and are a potentially causal cell type underpinning genetic associations with immune system traits and diseases. Here, we profile the binding of myeloid master regulator PU.1 in primary neutrophils across nearly a hundred volunteers. We show that variants associated with differential PU.1 binding underlie genetically-driven differences in cell count and susceptibility to autoimmune and inflammatory diseases. We integrate these results with other multi-individual genomic readouts, revealing coordinated effects of PU.1 binding variants on the local chromatin state, enhancer-promoter contacts and downstream gene expression, and providing a functional interpretation for 27 genes underlying immune traits. Collectively, these results demonstrate the functional role of PU.1 and its target enhancers in neutrophil transcriptional control and immune disease susceptibility.

Circular RNA Foxo3: A Promising Cancer-Associated Biomarker

Circular RNAs (circRNAs) are a class of novel non-coding RNAs (ncRNAs). Emerging evidence demonstrates that circRNAs play crucial roles in many biological processes by regulating linear RNA transcription, downstream gene expression and protein or peptide translation. Meanwhile, recent studies have suggested that circRNAs have the potential to be oncogenic or anti-oncogenic and play vital regulatory roles in the initiation and progression of tumors. Circular RNA Forkhead box O3 (circ-Foxo3, hsa_circ_0006404) is encoded by the human FOXO3 gene and is one of the most studied circular RNAs acting as a sponge for potential microRNAs (miRNAs) (Du et al., 2016). Previous studies have reported that circ-Foxo3 is involved in the development and tumorigenesis of a variety of cancers (bladder, gastric, acute lymphocytic leukemia, glioma, etc.). In this review, we summarize the current studies concerning circ-Foxo3 deregulation and the correlative mechanism in various human cancers. We also point out the potential clinical applications of this circRNA as a biomarker for cancer diagnosis and prognosis.