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.

Venous congestion and volume overload are important in cardiorenal syndromes, in which multiple regulated factors are involved, including long non-coding RNAs (lncRNAs). To investigate the underlying role of lncRNAs in regulating the development of venous congestion, an Affymetrix microarray associated with peripheral venous congestion was annotated, then a bipartite dynamic lncRNA-mRNA co-expression network was constructed in which nodes indicated lncRNAs or mRNAs. The nodes were connected when the lncRNAs or mRNAs were dynamically co-expressed. Following functional analysis of this network, several dynamic alternative pathways were identified, including the calcium signaling pathway during venous congestion development. Additionally, certain lncRNAs (LINC00523, LINC01210 and RP11-435O5.5) were identified that may potentially dynamically regulate certain proteins, including plasma membrane calcium ATPase (PMCA) and G protein-coupled receptor (GPCR), in the calcium signaling pathway. Particularly, the dynamically regulated switch of LINC00523 from co-expression with PMCA to GPCR may be involved in damage to steady state intracellular calcium. In brief, the current study demonstrated a potential novel mechanism of lncRNA function during venous congestion.

miR-30b, which is encoded by the gene located on chromosome 8q24.22, plays an important role in a variety of diseases. In most types of tumors, miR-30b significantly inhibits the proliferation, migration, and invasion of cancer cells through the regulation of target genes. Moreover, miR-30b can inhibit the PI3K/AKT signaling pathway through the regulation of EGFR, AKT, Derlin-1, GNA13, SIX1, and other target genes, thus inhibiting the EMT process of tumor cells and promoting apoptosis. In addition, miR-30 plays a significant role in alleviating drug resistance in tumor cells. Although the use of miR-30b as a clinical diagnostic indicator or anticancer drug is still facing great difficulties in the short term, with the deepening of research, the potential application of miR-30b is emerging.

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Gastric cancer is the fifth most frequently occurring and the fourth most lethal malignant cancer worldwide. A bioactive protein (pPe O p) from Omphalia lapidescens exhibits significant inhibitory effects on gastric cancer cells. miRNA deep sequencing analysis shows that miR-30b-5p is significantly upregulated in HGC-27 cells treated with pPe O p. Verification results show that the expression level of miR-30b-5p is significantly increased in HGC-27 cells after pPe O p treatment. Additionally, miR-30b-5p is significantly downregulated in clinical gastric cancer tissues compared to that in adjacent normal tissues. Following pPe O p treatment and/or transfection with miR-30b-5p mimic, the proliferation, migration, and invasion of HGC-27 cells are significantly impaired. Immunofluorescence microscopy shows that pPe O p and/or miR-30b-5p destroy(s) microfilaments and microstructures and inhibit(s) the formation of pseudopodia. Bioinformatics analysis, dual-luciferase reporter assay, and western blot analysis confirm that miR-30b-5p downregulates Rac1/Cdc42 expression and activation by targeting RAB22A. Available data indicate that miR-30b-5p plays an anti-gastric cancer role in mediating pPe O p. pPe O p upregulates miR-30b-5p expression, which in turn inhibits RAB22A expression, resulting in a reduction in the expression and activation of Rac1 and Cdc42 and their downstream targets, thus destroying the cytoskeletal structure and inhibiting the proliferation, migration, and invasion of cancer cells.