MiR-509-3p promotes gastric cancer development by activating FOXM1-mediated p38/MK2 pathway.

Gastric cancer (GC), a malignant tumor, is highly prevalent, particularly in Asia. miR-509-3p plays a crucial role in regulating tumorigenesis, but its mechanism in GC remains unclear. Potential targets of miR-509-3p were identified through database analysis (miRWalk, TargetScan, ENCORI, and TCGA). The binding site between miR-509-3p and forkhead box protein M1 (FOXM1) was confirmed using a dual-luciferase assay. CCK-8, EdU, Transwell, wound healing assays, flow cytometry, and Western blot analysis were employed to examine changes in proliferation, migration, invasion, apoptosis, FOXM1, and the p38 MAPK (p38)/MAPK-activated protein kinase 2 (MK2) pathway in GC cells (MNK-45 and HGC-27) after miR-509-3p overexpression or knockdown, FOXM1 overexpression, and application of the p38 pathway agonist Anisomycin. The size and weight of subcutaneous xenografts were measured, and the effects of miR-509-3p overexpression were analyzed through histopathological staining (Tunel immunofluorescence, HE staining, Ki67, and FOXM1 immunohistochemistry). The results showed that overexpression of miR-509-3p suppressed proliferation, migration, and invasion while accelerating apoptosis. Knockdown of miR-509-3p promoted malignant progression. miR-509-3p inhibited GC by regulating FOXM1-mediated p38/MK2 pathway activation, and miR-509-3p mimics restrained tumor growth in vivo through this pathway. In conclusion, miR-509-3p suppresses GC malignant progression by regulating FOXM1-mediated p38/MK2 pathway activation.

Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway.

We evaluated the expression profiles of differentially expressed miRNAs (DEmiRNAs) involved in human fetal skin development via high-throughput sequencing to explore the expression difference and the regulatory role of miRNA in different stages of fetal skin development. Analysis of expression profiles of miRNAs involved collecting embryo samples via high-throughput sequencing, then bioinformatics analyses were performed to validate DEmiRNAs. A total of 363 miRNAs were differentially expressed during the early and mid-pregnancy of development, and upregulated DEmiRNAs were mainly concentrated in the let-7 family. The transfection of let-7b-5p slowed down HaCaT cell proliferation and promoted apoptosis, as evidenced by the cell counting kit-8 assay, quantitative real-time polymerase chain reaction, and flow cytometry. The double luciferin reporter assay also confirmed let-7b-5p and ΔNp63 downregulation through the combination with the 3'-untranslated region of ΔNp63. Moreover, treatment with a let-7b-5p inhibitor upregulated ΔNp63 and activated the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. The let-7b-5p caused a converse effect on HaCaT cells because of Np63 upregulation. Let-7b-5p regulates skin development by targeting ΔNp63 via PI3K-AKT signaling, contributing to future studies on skin development and clinical scar-free healing.

Comprehensive analysis of the aberrantly expressed lncRNA­associated ceRNA network in breast cancer.

Previous studies have suggested that long non­coding RNAs (lncRNAs) are closely associated with human diseases, particularly cancer, including cancer of the lung, breast and stomach. A variety of lncRNAs are abnormally expressed in cancer and participate in several pathways including cell proliferation and apoptosis; these elements are closely associated with the development of cancer. The Cancer Genome Atlas (TCGA) is an important cancer database. It consists of clinical data, genomic variation, mRNA, microRNA (miRNA) and lncRNAs expression, methylation and other data for various types of human cancer. In the present study, differential expression of RNA was identified using the edgeR package. A total 1,222 RNA sequencing profiles from patients with breast cancer were downloaded from TCGA. A competing endogenous RNA (ceRNA) network was constructed for breast cancer based on miRcode and miRTarBase. The top 10 lncRNAs were selected using Cox regression analysis. Survival analysis was performed using Kaplan­Meier analysis. A total of 1,028 breast cancer­associated lncRNAs and 89 miRNAs (fold change >2; P<0.05) were identified; among these, 93 lncRNAs and 19 miRNAs were included in the ceRNA network. Subsequently, 10 basic lncRNAs were selected and their associations with overall survival were identified. In addition, 5 lncRNAs (ADAM metallopeptidase with thrombospondin type 1 motif 9­antisense RNA 1, AL513123.1, chromosome 10 open reading frame 126, long intergenic non­protein coding RNA 536 and Wilms tumor 1 antisense RNA) were identified to be significantly associated with overall survival (P<0.05, log rank test). These results suggested that mRNAs, lncRNAs and miRNAs were involved in pathological mechanisms of breast cancer. The newly­identified ceRNA network included 93 breast cancer­specific lncRNAs, 19 miRNAs and 27 mRNAs. The results of the present study highlight the potential of lncRNAs in understanding the development and pathogenesis of breast cancer, and suggest novel concepts and an experimental basis for the identification of prognostic biomarkers and therapeutic targets for breast cancer.