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Background. Rheumatoid arthritis (RA) is the most common autoimmune disease and affects multiple joints. Previous studies have shown that total saponins of Radix clematidis (TSC) have a clear therapeutic effect on RA, but the specific mechanism has not yet been clarified. Literature screening and previous research suggest that the lncRNA OIP5-AS1/miR-410-3p/Wnt7b signaling pathway exerts a regulatory effect on the pathogenesis of RA. In this study, we examined whether the TSC treatment of RA affects the lncRNA OIP5-AS1/miR-410-3p/Wnt7b pathway. Materials and Methods. Freund's complete adjuvant was used to create an adjuvant arthritis (AA) rat model with rat synovial cells being harvested and cultured. The experiment comprises a normal group, model group, TSC optimal-dose group, TSC optimal-dose group + lncRNA OIP5-AS1siRNA group, lncRNA OIP5-AS1 siRNA group, and lncRNA OIP5-AS1 siRNA + NC group. MMT was used to screen the optimal concentration of TSC. The level of lncRNA OIP5-AS1, miR-410-3p, Wnt7b, β-catenin, c-Myc, cyclin D1, GSK-3β, and SFRP4 mRNA were detected by real-time-qPCR, the expression of Wnt7b, β-catenin, c-Myc, cyclin D1, GSK-3β, and p-GSK-3β (Ser9) protein were detected by immunofluorescence and Western blot. Results. We found that TSC inhibits the proliferation of RA FLS, TSC significantly reduced lncRNA OIP5-AS1, Wnt7b, β-catenin, c-Myc, cyclin D1, and p-GSK-3β/GSK-3β mRNA/protein expression, whereas the miR-410-3p and SFRP4 mRNA/protein expression levels were significantly upregulated. Our data suggest that TSC can inhibit the excessive proliferation of FLS to treat RA, the mechanism of which may be closely related to regulation of the lncRNA OIP5-AS1/miR-410-3p /Wnt7b signaling axis and the Wnt signaling pathway. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC), as an epidemic cancer worldwide, has more than 1 million new cases and an estimated 769,000 deaths worldwide in 2020, ranking fifth and fourth in global morbidity and mortality. In mammals, both miRNAs and transcription factors (TFs) play a partial role in gene expression regulation. The mRNA expression profile and miRNA expression profile of GEO database were screened by GEO2R for differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs). Then, DAVID annotated the functions of DEGs to understand the functions played in biological processes. The prediction of potential target genes of miRNA and key TFs of mRNA was performed by mipathDB V2.0 and CHEA3, respectively, and the gene list comparison was performed to look for overlapping genes coregulated by key TFs and DEMs. Finally, the obtained miRNAs, TF, and overlapping genes were used to construct the miRNA-mRNA-TF regulatory network, which was verified by RT-qPCR. 76 upregulated DEGs, 199 downregulated DEGs, and 3 upregulated miRNAs (miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p) were identified from the expression profiles of mRNA (GSE26899, GSE29998, GSE51575, and GSE13911) and miRNA (GSE93415), respectively. Through database prediction and gene list comparison, it was found that among the 199 downregulated DEGs, 61, 71, and 69 genes were the potential targets of miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p, respectively. 199 downregulated DEGs were used as the gene list for the prediction of key TFs, and the results showed that RFX6 ranked the highest. The potential target overlap genes of miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p were 4 genes (SH3GL2, ATP4B, CTSE, and SORBS2), 7 genes (SLC7A8, RNASE4, ESRRG, PGC, MUC6, Fam3B, and FMO5), and 6 genes (CHGA, PDK4, TMPRSS2, CLIC6, GPX3, and PSCA), respectively. Finally, we constructed a miRNA-mRNA-TF regulatory network based on the above 17 mRNAs, 3 miRNAs, and 1 TF and verified by RT-qPCR and western blot results that the expression of RFX6 was downregulated in GC tissues. These identified miRNAs, mRNAs, and TF have a certain reference value for further exploration of the regulatory mechanism of GC. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNA/miRs) have been demonstrated to be critical post-transcriptional modulators of gene expression during tumorigenesis. Numerous miRNAs have been revealed to be downregulated in human epithelial ovarian cancer (EOC). In the present study, it was observed that the expression of miR-145 was decreased in EOC tissues and cell lines. Overexpression of miR-145 inhibited the proliferation, migration and invasion of EOC cells. The D-type cyclin 2, cyclin D2 (CCND2), and E2F transcription factor 3 (E2F3) were confirmed to be targets of miR-145. In addition, restoration of these 2 genes significantly reversed the tumor suppressive effects of miR-145. Collectively, the results indicated that miR-145 serves a critical role in suppressing the biological behavior of EOC cells by targeting CCND2 and E2F3. Therefore, miR-145 was suggested to be a potential miRNA-based therapeutic target in ovarian cancer. [ABSTRACT FROM AUTHOR]

Low temperature affects plant growth and crop productivity. The CBF genes are a class of transcription factors that play important roles in cold response. Here we report that AtMYB14 participates in freezing tolerance in Arabidopsis by affecting expression of CBF genes. The AtMYB14 gene was down-regulated by cold treatment. AtMYB14 encodes a nuclear protein that functions as an R2R3-MYB transcription activator. Knock-down of AtMYB14 by artificial microRNA increased the tolerance to freezing stress. Both the CBF genes and the downstream genes were induced to a much higher level in AtMYB14 knock-down plants than in wild type under cold treatment. Our results suggest that AtMYB14 plays an important role in the plant response to cold stress. [ABSTRACT FROM AUTHOR]

Aberrant activations of Hedegehog (Hh) signaling were found in hepatocellular carcinoma (HCC) and some other cancer types. However, the details have not been completely understood and the underlying mechanism remains unclear. Here we reported that miR-1249 transcription in HCC cells was regulated through direct binding to the conserved sequences in miR-1249 promoter region by Gli1, which functions as a transcription factor and is a component in the Hh signaling pathway. Interestingly, expression of tumor suppressor PTCH1, which is another component of the Hh signaling pathway, was inhibited by miR-1249 through targeting its 3′-untranslated region. Down-regulation of PTCH1 further enhanced the downstream effects mediated by Gli1. In consistent with these findings, miR-1249 expression level was correlated with degree of prognosis (p=0.005) in HCC patients. Taken together, our results suggested the existence of a positive feedback loop comprised of Gli1, miR-1249 and PTCH1. During the process of HCC progression, this positive feedback loop could be continuously activated to enhance tumor cell growth, migration and invasion. [ABSTRACT FROM AUTHOR]