Alternative splicing (AS), an essential process for the maturation of mRNAs, is involved in tumorigenesis and tumor progression, including angiogenesis, apoptosis, and metastasis. AS changes can be frequently observed in different tumors, especially in geriatric lung adenocarcinoma (GLAD). Previous studies have reported an association between AS events and tumorigenesis but have lacked a systematic analysis of its underlying mechanisms. In the present study, we obtained splicing event information from SpliceSeq and clinical information regarding GLAD from The Cancer Genome Atlas. Survival-associated AS events were selected to construct eight prognostic index (PI) models. We also constructed a correlation network between splicing factors (SFs) and survival-related AS events to identify a potential molecular mechanism involved in regulating AS-related events in GLAD. Our study findings confirm that AS has a strong prognostic value for GLAD and sheds light on the clinical significance of targeting SFs in the treatment of GLAD.

The relationship between mechanical force and alveolar bone remodeling is an important issue in orthodontics because tooth movement is dependent on the response of bone tissue to the mechanical force induced by the appliances used. Mechanical cyclical stretch plays an essential role in the cell osteogenic differentiation involved in bone remodeling. However, the underlying mechanisms are unclear, particularly the molecular pathways regulated by mechanical stimulation. In the present study, we reported a dynamic change of p21 level in response to mechanical cyclical stretch, and shRNA-p21 in bone marrow mesenchymal stem cells (BMSCs) induced osteogenic differentiation. The mechanism was mediated through TWIST/E2A/p21 axis. These results supported the mechanical stimulation-induced osteogenic differentiation is negatively regulated by p21.

Triple negative breast cancer (TNBC) is a more common type of breast cancer with high distant metastasis and poor prognosis. The potential role of lamins in cancer progression has been widely revealed. However, the function of lamin B2 (LMNB2) in TNBC progression is still unclear. The present study aimed to investigate the role of LMNB2 in TNBC. The cancer genome atlas (TCGA) database analysis and immunohistochemistry (IHC) were performed to examine LMNB2 expression levels. LMNB2 short hairpin RNA plasmid or lentivirus was used to deplete the expression of LMNB2 in human TNBC cell lines including MDA-MB-468 and MDA-MB-231. Alterations in cell proliferation and apoptosis in vitro and the nude mouse tumorigenicity assay in vivo were subsequently analyzed. The human TNBC tissues shown high expression of LMNB2 according to the bioinformation analysis and IHC assays. LMNB2 expression was correlated with the clinical pathological features of TNBC patients, including pTNM stage and lymph node metastasis. Through in vitro and in vivo assays, we confirmed LMNB2 depletion suppressed the proliferation and induced the apoptosis of TNBC cells, and inhibited tumor growth of TNBC cells in mice, with the decrease in Ki67 expression or the increase in caspase-3 expression. In conclusion, LMNB2 may promote TNBC progression and could serve as a potential therapeutic target for TNBC treatment.

MicroRNA (MiR)-942 regulates the development of a variety of tumors, however, its function in breast cancer (BCa) has been less reported. Therefore, the present study investigated the regulatory effects of miR-942 on BCa cells. The expression of miR-942 in whole blood samples and BCa cell lines was detected by quantitative real-time (qRT)-PCR. Direct target gene for miR-942 was confirmed by dual-luciferase reporter assay. FOXA2 expression in adjacent tissues was detected by qRT-PCR. The effects of miR-942, or miR-942 with FOXA2, on the cell viability, proliferation, apoptosis, migration and invasion of BCa cells were determined by cell counting kit-8 (CCK-8), colony formation assay, flow cytometry, wound scratch and Transwell, respectively. The levels of N-Cadherin, E-Cadherin and Snail were determined by Western blot. Kaplan-Meier was used to explore the relationship among the expressions of miR-942 and FOXA2 and the prognosis of BCa patients. MiR-942 had high expressed in BCa, while its low expression significantly suppressed the cell viability, proliferation, migration and invasion of BCa, but increased cell apoptosis. Down-regulation of N-Cadherin and Snail and up-regulation of E-Cadherin were also induced by low-expression of miR-942. FOXA2, which was proved as the direct target gene for miR-942 and was low-expressed in BCa, partially reversed the effect of overexpressed miR-942 on promoting cell viability, proliferation, migration and invasion, and suppressed cell apoptosis. A lower survival rate was observed in BCa patients with a high expression of miR-942 and a low expression of FOXA2. MiR-942 promoted the progression of BCa by down-regulating the expression of FOXA2.

Necrotizing enterocolitis (NEC) is a critical neonatal disease with a high mortality. The possibility that miRNAs may play an important role in NEC has raised great attention. Hence, the present study identified biomarkers that affected NEC in newborn progression through miRNA and gene expression profile analysis. miRNA chip GSE68054 and gene chip GSE46619 of NEC in newborn were analyzed to screen out differentially expressed miRNA and differentially expressed genes (DEGs). Next, target genes of differentially expressed miRNA were predicted, and differentially expressed miRNA-DEG regulatory network was constructed to select key miRNAs. After gene ontology and kyoto encyclopedia of genes and genomes enrichment analysis on target genes of key miRNAs, the target genes enriched in pathways were extracted to establish differentially expressed miRNA-DEG-disease gene network for gene interaction analysis. Targetting relationship between miRNAs and target genes was verified. A total of 15 miRNAs were differentially expressed in NEC in newborn, amongst which miR-429/200a/b and miR-141/200c clusters were poorly expressed and might play a significant role in NEC in newborn. Besides, target genes of miR-429/200a/b and miR-141/200c clusters were enriched in 11 signaling pathways. Vascular endothelial growth factor (VEGFA), E-selectin (SELE), kinase insert domain receptor (KDR), fms-related tyrosine kinase 1 (FLT1), and hepatocyte growth factor (HGF) were highly expressed in NEC in newborn, which were negatively regulated by miR-429/200a/b and miR-141/200c clusters and shared close association with disease genes. miR-429/200a/b and miR-141/200c clusters are poorly expressed while their target genes (VEGFA, SELE, KDR, FLT1, and HGF) are highly expressed in NEC in newborn, which might be identified as important biomarkers for this disease.

LncRNA LINC00657 has oncogenic or anti-carcinoma roles in different cancers, and yet its detailed molecular mechanism in esophageal cancer (EC) remains unclear. In addition, competitive endogenous RNA (ceRNA) regulatory lncRNA-miRNA-mRNA networks are critical for tumorigenesis and progression. Hence, the present study explored the roles of LINC00657 in EC and identified its relevant ceRNA network. We first detected the expression of LINC00657 in EC. Then, we applied starBase and TargetScan websites to find miR-26a-5p binding to LINC00657 and obtain CKS2 as a target of miR-26a-5p. The roles of LINC00657, miR-26a-5p or CKS2 in the proliferation, migration, invasion, and apoptosis of EC cells were respectively assessed by CCK-8, wound healing assay, transwell invasion assay, and flow cytometry. The changes of the MDM2/p53/Bcl2/Bax pathway were measured via Western blot. The results revealed that LINC00657 showed an aberrant high expression in EC cells, which promoted the growth of EC cells. Additionally, LINC00657 functioned as a sponge of miR-26a-5p, and LINC00657 negatively mediated miR-26a-5p to regulate the growth of EC cells. Furthermore, CKS2 was observed as a direct target of miR-26a-5p, and CKS2 controlled the growth of EC cells via the MDM2/p53/Bcl2/Bax pathway. Moreover, there was a positive correlation between LINC00657 and CKS2. LINC00657 knockdown inhibited CKS2 expression to suppress the proliferation, migration, and invasion of EC cells and induced apoptosis via regulating the MDM2/p53/Bcl2/Bax pathway. Collectively, LINC00657/miR-26a-5p/CKS2 ceRNA network could promote the progression of EC, which is good for understanding the molecular mechanism of EC and offers novel biomarkers for EC diagnosis and therapy.

The present study aimed to identify the gene expression changes conferred by capsaicin in the cell model of 6-OHDA-induced Parkinson's disease, to disclose the molecular mechanism of action of capsaicin. We used capsaicin-treated and paraffin-embedded wax blocks containing substantia nigra tissue from 6-OHDA-induced Parkinson's disease rats to analyze transcriptional changes using Affymetrix GeneChip Whole Transcript Expression Arrays. A total of 108 genes were differentially expressed in response to capsaicin treatment, and seven of these genes were selected for further analysis: Olr724, COX1, Gsta2, Rab5a, Potef, Actg1, and Acadsb, of which Actg1 (actin gamma 1) was down-regulated and Gsta2 (Glutathione S-transferase alpha 2) was up-regulated. We successfully overexpressed Actg1 and Gsta2 in vitro. CCK-8 detection and flow cytometry demonstrated that overexpression of Actg1 and Gsta2 increased apoptosis in the 6-OHDA-induced Parkinson's disease cell model. The imbalance between Actg1 and Gsta2 may be one of the mechanisms of cell damage in Parkinson's disease (PD). Capsaicin can protect the cells and reduce the apoptosis rate by regulating Actg1 and Gsta2.

XiaoLuoWan (XLW) is a classical formula in traditional Chinese medicine (TCM) that has satisfactory therapeutic effects for uterine fibroids (UFs). However, its underlying mechanisms remain unclear. To elucidate the pharmacological actions of XLW in treating UFs, an ingredient-target-disease framework was proposed based on network pharmacology strategies. The active ingredients in XLW and their putative targets were obtained from the TCM systems pharmacology database and analysis platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) platforms. The known therapeutic targets of UFs were acquired from the DigSee and DrugBank databases. Then, the links between putative XLW targets and therapeutic UF targets were identified to establish interaction networks by Cytoscape. Finally, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of overlapping gene targets were performed in the STRING database and visualized in R software. In total, 9 active compounds were obtained from 74 ingredients, with 71 curative targets predicted in XLW. Moreover, 321 known therapeutic targets were closely related to UFs, with 29 targets overlapping with XLW and considered interacting genes. Pathway enrichment revealed that the calcium signaling pathway was significantly enriched and the mitogen-activated protein kinase (MAPK) signaling pathway, cAMP signaling pathway, cancer and vascular smooth muscle contraction pathways, cGMP-PKG signaling pathway, and AGE-RAGE signaling pathway were closely associated with XLW intervention for UFs. In conclusion, the network pharmacology detection identified 9 available chemicals as the active ingredients in XLW that may relieve UFs by regulating 29 target genes involved in the calcium signaling pathway, MAPK pathway and cAMP pathway. Network pharmacology analyses may provide more convincing evidence for the investigation of classical TCM prescriptions, such as XLW.

The aims of the present study were to explore immune-related genes (IRGs) in stage IV colorectal cancer (CRC) and construct a prognostic risk score model to predict patient overall survival (OS), providing a reference for individualized clinical treatment.