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Objective. To analyze the mechanism of LINC00461 regulating the recurrence of diffuse large B cell lymphoma (DLBCL) through microRNA (miR)-411-5p/BCL2 interacting protein 3 (BNIP3) pathway. Methods. DLBCL samples in TCGA and GSE12453 were used for differential analysis to find long noncoding RNA (lncRNA) related to DLBCL recurrence. The 4 DLBCL data with the highest and lowest expression levels of LINC00461 in the TCGA database were selected for GSEA enrichment analysis. The targeting relationships of miR-411-5p with LINC00461 and BNIP3 were verified by the dual luciferase report. Blood samples from DLBCL patients were used to analyze the correlation between miR-411-5p and LINC00461 or BNIP3. LINC00461, miR-411-5p, or BNIP3 was overexpressed or silenced by transfection, and a tumor-bearing nude mice model was constructed to detect their effects on proliferation and apoptosis. Results. The level of LINC00461 in DLBCL was significantly higher than that in normal cases, and the level in recurrence DLBCL was significantly higher than that in nonrecurrence. The enrichment analysis results showed that the function of LINC00461 was closely related to apoptosis. The results shown that miR-411-5p bound to LINC00461 and BNIP3 and was negatively correlated with LINC00461 and BNIP3 mRNA in blood of DLBCL patients. Suppressing the level of LINC00461 inhibited cell proliferation and induced apoptosis. The inhibition of LINC00461 or overexpression of miR-411-5p reduced the expression of BNIP3 protein, thereby inducing apoptosis at the in vivo and in vitro levels. Conclusion. LINC00461 may induce miR-411-5p to "sponge," thereby increasing the expression of BNIP3 protein, and exerting the function of inhibiting apoptosis and promoting DLBCL recurrence. [ABSTRACT FROM AUTHOR]

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]

The biological function of human ovaries declines along with aging. To identify the underlying molecular changes during ovarian aging, pigs were used as model animals. Genome-wide DNA methylation and transcriptome-wide RNA expression analyses were performed via high-throughput sequencing of ovaries from young pigs (180 days, puberty stage of first ovulation) and old pigs (eight years, reproductive exhaustion stage). The results identified 422 different methylation regions between old and young pigs; furthermore, a total of 2,243 mRNAs, 95 microRNAs, 248 long noncoding RNAs (lncRNAs), and 116 circular RNAs (circRNAs) were differentially expressed during both developmental stages. Gene ontology analysis showed that these genes related to different methylation and expression are involved in the ovarian aging cycle. Specifically, these are involved in cell apoptosis, death effector domain binding, embryonic development, reproduction and fertilization process, ovarian cumulus expansion, and the ovulation cycle. Multigroup cooperative control relationships were also assessed, and competing endogenous RNA (ceRNA) networks were constructed in the ovarian aging cycle. These data will help to clarify ovary age-associated potential molecular changes in DNA methylation and transcriptional patterns over time. [ABSTRACT FROM AUTHOR]