Kirkpatrickstorgaard0323

In summary, our findings demonstrate a critical role of H19-modulated SNORA7A expression in LFS-associated osteosarcomas.Background Mendelian randomization (MR) provides unconfounded estimates. MR is open to selection bias when the underlying sample is selected on surviving to recruitment on the genetically instrumented exposure and competing risk of the outcome. Few methods to address this bias exist. Methods We show that this selection bias can sometimes be addressed by adjusting for common causes of survival and outcome. We use multivariable MR to obtain a corrected MR estimate for statins on stroke. Statins affect survival, and stroke typically occurs later in life than ischemic heart disease (IHD), making estimates for stroke open to bias from competing risk. Results In univariable MR in the UK Biobank, genetically instrumented statins did not protect against stroke [odds ratio (OR) 1.33, 95% confidence interval (CI) 0.80-2.20] but did in multivariable MR (OR 0.81, 95% CI 0.68-0.98) adjusted for major causes of survival and stroke [blood pressure, body mass index (BMI), and smoking initiation] with a multivariable Q-statistic indicating absence of selection bias. However, the MR estimate for statins on stroke using MEGASTROKE remained positive and the Q statistic indicated pleiotropy. Conclusion MR studies of harmful exposures on late-onset diseases with shared etiology need to be conceptualized within a mechanistic understanding so as to identify any potential bias due to survival to recruitment on both genetically instrumented exposure and competing risk of the outcome, which may then be investigated using multivariable MR or estimated analytically and results interpreted accordingly.Sex-linked dwarf (SLD) chicken, which is caused by a recessive mutation of the growth hormone receptor (GHR), has been widely used in the Chinese broiler industry. However, it has been found that the SLD chicken has more abdominal fat deposition than normal chicken. Excessive fat deposition not only reduced the carcass quality of the broilers but also reduced the immunity of broilers to diseases. selleck inhibitor To find out the key genes and the precise regulatory pathways that were involved in the GHR mutation-induced excessive fat deposition, we used high-fat diet (HFD) and normal diet to feed the SLD chicken and normal chicken and analyzed the differentially expressed genes (DEGs) among the four groups. Results showed that the SLD chicken had more abdominal fat deposition and larger adipocytes size than normal chicken and HFD can promote abdominal fat deposition and induce adipocyte hypertrophy. RNA sequencing results of the livers and abdominal fats from the above chickens revealed that many DEGs between the SLD and normosition of the SLD chicken and reveals that SOCS2 and CISH are two key genes involved in the GHR mutation-induced excessive fat deposition of the SLD chicken.Increasing lncRNA-associated competing triplets were found to play important roles in cancers. With the accumulation of high-throughput sequencing data in public databases, the size of available tumor samples is becoming larger and larger, which introduces new challenges to identify competing triplets. Here, we developed a novel method, called LncMiM, to detect the lncRNA-miRNA-mRNA competing triplets in ovarian cancer with tumor samples from the TCGA database. In LncMiM, non-linear correlation analysis is used to cover the problem of weak correlations between miRNA-target pairs, which is mainly due to the difference in the magnitude of the expression level. In addition, besides the miRNA, the impact of lncRNA and mRNA on the interactions in triplets is also considered to improve the identification sensitivity of LncMiM without reducing its accuracy. By using LncMiM, a total of 847 lncRNA-associated competing triplets were found. All the competing triplets form a miRNA-lncRNA pair centered regulatory network, in which ZFAS1, SNHG29, GAS5, AC112491.1, and AC099850.4 are the top five lncRNAs with most connections. The results of biological process and KEGG pathway enrichment analysis indicates that the competing triplets are mainly associated with cell division, cell proliferation, cell cycle, oocyte meiosis, oxidative phosphorylation, ribosome, and p53 signaling pathway. Through survival analysis, 107 potential prognostic biomarkers are found in the competing triplets, including FGD5-AS1, HCP5, HMGN4, TACC3, and so on. LncMiM is available at https//github.com/xiaofengsong/LncMiM.

Hepatocellular carcinoma (HCC) is one of the most common types of cancer that is associated with poor quality of life in patients and a global health burden. The mechanisms involved in the development and progression of HCC remain poorly understood.

Hepatocellular carcinoma human samples and cell lines were subjected to qRT-PCR for expression assessment. CCK-8 assay, Transwell migration and invasion assay, were applied for cell function detection. Animal experiment was used to measure the function of SNHG17 on cell growth

. Western blot was conducted to evaluate the level of EMT in cells. RIP, RNA pull-down and luciferase reporter assays were performed to assess the correlation between SNHG17, miR-3180-3p and RFX1.

Our study demonstrated that SNHG17 was upregulated in HCC human samples and involved cell proliferation, migration, invasion progress. SNHG17 promoted HCC cell growth and metastasis

. Furthermore, we investigated the downstream factor of SNHG17, SNHG17 acted as a molecular sponge for miR-3180-3p, and SNHG17 regulated RFX1 expression via miR-3180-3p. SNHG17 promotes tumor-like behavior in HCC cells via miR-3180-3p/RFX1.

We determined RFX1 as the target of miR-3810-3p; SNHG17 enhanced the progression of HCC via the miR-3180-3p/RFX1 axis. Taken together, our findings may provide insight into the molecular mechanism involved in the progression of HCC and develop SNHG17 as a novel therapeutic target against HCC.

We determined RFX1 as the target of miR-3810-3p; SNHG17 enhanced the progression of HCC via the miR-3180-3p/RFX1 axis. Taken together, our findings may provide insight into the molecular mechanism involved in the progression of HCC and develop SNHG17 as a novel therapeutic target against HCC.The emerald ash borer (EAB), Agrilus planipennis, is a highly destructive quarantine pest. The olfactory and visual systems of A. planipennis play different but critical roles at newly emerged and sexually mature stages; however, the molecular basis underlying these differences remain unclear. Consequently, based on deep transcriptome sequencing, we evaluated the expression levels of chemosensory-related proteins and opsins at the two developmental stages of A. planipennis. We found 15 new chemosensory-related genes in our transcriptome assembly compared with the previous genome assembly, including 6 that code for odorant-binding proteins (OBPs) and 9 for chemosensory proteins (CSPs). The expression of several chemosensory-related genes (OBP7, OBP10, CSP1, and CSP12) differed markedly between newly emerged and sexually mature A. planipennis. We also found that the expression of UV opsin 2 and LW opsin 1 was higher in sexually mature male A. planipennis, which may be associated with their strong visual mate detection ability. This study forms the basis for further investigation of the chemosensory and visual system of A. planipennis, and these differentially expressed genes between newly emerged and sexually mature stages may serve as targets for the management of this destructive forest pest after sexual maturity.

Triple-negative breast cancer (TNBC) is a type of breast cancer (BC) showing a high recurrence ratio and a low survival probability, which requires novel actionable molecular targets. The involvement of alternative splicing (AS) in TNBC promoted us to study the potential roles of AS events in the survival prognosis of TNBC patients.

A total of 150 TNBC patients from The Cancer Genome Atlas (TCGA) were involved in this work. To study the effects of AS in the recurrence-free survival (RFS) prognosis of TNBC, we performed the analyses as follows. First, univariate Cox regression model was applied to identify RFS-related AS events. Their host genes were analyzed by Metascape to discover the potential functions and involved pathways. Next, least absolute shrinkage and selection operator (LASSO) method was used to select the most informative RFS-related AS events to constitute an AS risk factor for RFS prognosis, which was evaluated by Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves in all e promising in the OS prognosis of TNBC as well.

The abnormal AS events regulated by SFs may act as a kind of biomarker for the survival prognosis of TNBC.

The abnormal AS events regulated by SFs may act as a kind of biomarker for the survival prognosis of TNBC.Growth, one of the most important traits monitored in domestic animals, is essentially associated with bone development. To date, no large-scale transcriptome studies investigating bone development in bighead carp have been reported. In this study, we applied Isoform-sequencing technology to uncover the entire transcriptomic landscape of the bighead carp (Hypophthalmichthys nobilis) in early growth stage, and obtained 63,873 non-redundant transcripts, 20,907 long non-coding RNAs, and 1,579 transcription factors. A total of 381 alternative splicing events were seen in the frontal and parietal bones with another 784 events simultaneously observed in the vertebral bones. Coupling this to RNA sequencing (RNA-seq) data, we identified 27 differentially expressed unigenes (DEGs) in the frontal and parietal bones and 45 DEGs in the vertebral bones in the fast-growing group of fish, when compared to the slow-growing group of fish. Finally, 15 key pathways and 20 key DEGs were identified and found to be involved in regulation of early growth such as energy metabolism, immune function, and cytoskeleton function and important cellular pathways such as the arginine and proline metabolic pathway (p4ha1), FoxO signaling pathway (sgk1), cell adhesion molecules (b2m, ptprc, and mhcII), and peroxisome proliferator-activated receptor signaling pathway (scd). We established a novel full-length transcriptome resource and combined it with RNA-seq to elucidate the mechanism of genetic regulation of differential growth in bighead carp. The key DEGs identified in this study could fuel further studies investigating associations between growth and bone development and serve as a source of potential candidate genes for marker-assisted breeding programs.The use of biological networks such as protein-protein interaction and transcriptional regulatory networks is becoming an integral part of genomics research. However, these networks are not static, and during phenotypic transitions like disease onset, they can acquire new "communities" (or highly interacting groups) of genes that carry out cellular processes. Disease communities can be detected by maximizing a modularity-based score, but since biological systems and network inference algorithms are inherently noisy, it remains a challenge to determine whether these changes represent real cellular responses or whether they appeared by random chance. Here, we introduce Constrained Random Alteration of Network Edges (CRANE), a method for randomizing networks with fixed node strengths. CRANE can be used to generate a null distribution of gene regulatory networks that can in turn be used to rank the most significant changes in candidate disease communities. Compared to other approaches, such as consensus clustering or commonly used generative models, CRANE emulates biologically realistic networks and recovers simulated disease modules with higher accuracy.