Construction of Adipogenic ceRNA Network Based on lncRNA Expression Profile of Adipogenic Differentiation of Human MSC Cells.

The Long non-coding RNA (lncRNA) expression profile data of ten samples including human Mesenchymal Stem Cell (MSC) adipogenic differentiation 0, 3, and 6 days from the GEO database, and then perform gene ID conversion, BLAST comparison, and annotation marking. Finally, group A (treatment group on day 3 of differentiation and control group on day 0 of differentiation) obtained a total of 1180 mRNA and 185 lncRNA; group B (treatment group on day 6 of differentiation and control group on day 0 of differentiation). A total of 1376 mRNA and 206 lncRNA were obtained. Finally, we processed the differential lncRNAs and mRNAs obtained in the two groups, and obtained 113 shared differential lncRNAs to further predict the targeted miRNA, a total of 815 lncRNA-miRNA pairs. The targeted mRNA was further predicted, and the grouped differential mRNAs were combined to obtain 64 differential mRNAs. In the end, we obtained 216 ceRNAs containing 26 lncRNAs, 27 miRNAs and 64 mRNAs. We found that the mRNAs in the ceRNA network were mainly enriched with 45 Gene Ontology (GO) terms, mainly including glucose homeostasis mechanism and insulin stimulation response. 69 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were mainly enriched. It mainly includes many pathways related to lipid metabolism such as Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), Rap1, cAMP, mitogen-activated protein kinase (MAPK), Ras, hypoxia inducible factor-1 (HIF-1), PI3K-Akt, insulin signaling and so on. In the end, we identified 216 ceRNA regulatory relationships related to obesity research. Our research provides a clearer direction for understanding the molecular mechanism of obesity, the screening and determination of drug targets biomarkers in the future.

Long Non-Coding RNAs of Plants in Response to Abiotic Stresses and Their Regulating Roles in Promoting Environmental Adaption.

Abiotic stresses triggered by climate change and human activity cause substantial agricultural and environmental problems which hamper plant growth. Plants have evolved sophisticated mechanisms in response to abiotic stresses, such as stress perception, epigenetic modification, and regulation of transcription and translation. Over the past decade, a large body of literature has revealed the various regulatory roles of long non-coding RNAs (lncRNAs) in the plant response to abiotic stresses and their irreplaceable functions in environmental adaptation. LncRNAs are recognized as a class of ncRNAs that are longer than 200 nucleotides, influencing a variety of biological processes. In this review, we mainly focused on the recent progress of plant lncRNAs, outlining their features, evolution, and functions of plant lncRNAs in response to drought, low or high temperature, salt, and heavy metal stress. The approaches to characterize the function of lncRNAs and the mechanisms of how they regulate plant responses to abiotic stresses were further reviewed. Moreover, we discuss the accumulating discoveries regarding the biological functions of lncRNAs on plant stress memory as well. The present review provides updated information and directions for us to characterize the potential functions of lncRNAs in abiotic stresses in the future.

F-box and leucine-rich repeat protein 16 controls tamoxifen sensitivity via regulation of mitochondrial respiration in estrogen receptor-positive breast cancer cells.

Tamoxifen is one of the most effective therapeutic tools for estrogen receptor-positive (ER +) breast cancer. However, the intrinsic insensitivity and resistance to tamoxifen remains a significant hurdle for achieving optimal responses and curative therapy. In this study, we report that F-box and leucine-rich repeat protein 16 (FBXL16) is located in the mitochondria of ER + breast cancer cells. The mitochondrial FBXL16 plays an essential role in sustaining mitochondrial respiration and thereby regulates the sensitivity of ER + breast cancer cells to tamoxifen treatment. Importantly, high FBXL16 expression is significantly correlated with poor overall survival of ER + breast cancer patients. Moreover, mitochondrial inhibition phenocopies FBXL16 depletion in terms of sensitizing the ER + breast cancer cells to tamoxifen treatment. Together, our study demonstrates that FBXL16 acts as a novel regulator of tamoxifen sensitivity. Thus, targeting FBXL16 may serve as a promising approach for improving the therapeutic efficacy of tamoxifen in ER + breast cancer cells.

CREB1 promotes proliferation and differentiation by mediating the transcription of CCNA2 and MYOG in bovine myoblasts.

The cAMP response element binding protein 1 (CREB1) is an important nuclear transcription factor in eukaryotes. To explore the potential role of CREB1 on Qinchuan bovine skeletal myoblasts, we investigated the function of CREB1 on proliferation and differentiation. In this study, we found that CREB1 promoted cell proliferation by promoting DNA synthesis in S phase and cell division in G2 phase and promoted myogenic differentiation process in bovine myoblasts. Through dual luciferase experiments, we found that CREB1 can bind to the proximal promoter regions of CCNA2 and MyoG, indicating that CREB1 can play a positive regulatory role in the proliferation and differentiation of myoblasts by mediating the transcription of CCNA2 and MyoG. In addition, through downstream target gene analysis and transcriptome sequencing, we found that CREB1 plays a role in cell proliferation, myogenic differentiation, skeletal muscle repair and other related pathways.

Online High-throughput Mutagenesis Designer Using Scoring Matrix of Sequence-specific Endonucleases.

CRISPR Cas9 and other sequence-specific endonucleases are fundamental genome editors supporting gene knockout and gene therapy. A speedy and accurate computational allele designer is required for a high through-put gene mutagenesis pipeline using these new techniques. An automatic system, Cas9 online designer (COD), was created to screen Cas9 targets and off-targets, as well as to provide gene knockout and genotyping strategies. A gene knockout rat model was successfully created and genotyped under the direction of this online system confirming its ability to predict real targets and off-targets. Gene knockout strategies to mutate 72 rat cytochrome P450 genes were designed instantly by the system to demonstrate its high-throughput efficiency. Also, the system used an off-target scoring matrix which can be applied to any sequence-specific genome editing tools besides Cas9. The COD system (http://cas9.wicp.net) has established a speedy, accurate, flexible and high through-put computational gene knockout pipeline supporting the sequence-specific endonuclease induced mutagenesis.