non-small cell lung cancer (nSclc) is a leading subtype of lung cancer, with high mortality rates. recently, long non-coding rnas (lncrnas) have been associated with nSclc. The present study aimed to examine the role of the TP73 antisense rna 1 (TP73-aS1) lncrna in nSclc. TP73-aS1 and microrna(mir)-34a-5p expression levels were measured using reverse transcription-quantitative Pcr (rT-qPcr) and chromogenic in situ hybridization (ciSH). cell proliferation, apoptosis, migration and invasion was determined using Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell and Matrigel assays, respectively. The median inhibitory concentration (ic 50) value of cisplatin (cis-diamminedichloroplatinum; ddP) was assessed using a ccK-8 assay. The interaction between mir-34a-5p and TP73-aS1 or tripartite motif-containing 29 (TriM29) was predicted using microrna. org and Starbase, then verified using a dual-luciferase reporter assay. The expression of TRIM29 was quantified at the mRNA and protein level using rT-qPcr and western blot analysis, respectively. TP73-AS1 was significantly upregulated, while mir-34a-5p was downregulated in nSclc tissues and cells. Functionally, TP73-aS1 knockdown inhibited proliferation, migration, invasion and ddP resistance, whilst inducing apoptosis in NSCLC cells. miR-34a-5p was identified as a target for TP73-aS1, and its inhibition reversed the effects of TP73-aS1 knockdown on nSclc cells. in addition, TriM29 was targeted by mir-34a-5p, and its overexpression reversed the effects of mir-34a-5p. Moreover, TP73-aS1 acted as a molecular sponge for mir-34a-5p, increasing the expression of TriM29. in conclusion, TP73-aS1 contributed to proliferation, migration and ddP resistance but inhibited apoptosis of nSclc cells by upregulating TriM29 and sponging mir-34a-5p.
BackgroundPioglitazone has been widely used as an insulin-sensitizing agent for improving glycemic control in patients with type 2 diabetes mellitus. However, cardiovascular risk and protective effects of pioglitazone remain controversial.ObjectivesIn this study, we investigated whether pioglitazone affects cardiomyocyte apoptosis and hypertrophy by regulating the VEGFR-2 signaling pathway.MethodsCardiomyocytes were enzymatically isolated from 1- to 3-day-old Sprague-Dawley rat ventricles. Effects of pioglitazone and the VEGFR-2-selective inhibitor apatinib on cardiomyocyte apoptotic rate was determined using flow cytometry, and hypertrophy was evaluated using [3H]-leucine incorporation. The protein expressions of unphosphorylated and phosphorylated VEGFR-2, Akt, P53, and mTOR were determined by Western-Blotting. Analysis of variance (ANOVA) was used to assess the differences between groups.ResultsPioglitazone and VEGFR-2-selective inhibitor apatinib reduced rat cardiomyocyte viability and cardiomyocyte hypertrophy induced by angiotensin II in vitro. Furthermore, in the same in vitro model, pioglitazone and apatinib significantly increased the expression of Bax and phosphorylated P53 and decreased the expression of phosphorylated VEGFR-2, Akt, and mTOR, which promote cardiomyocyte hypertrophy.ConclusionsThese findings indicate that pioglitazone induces cardiomyocyte apoptosis and inhibits cardiomyocyte hypertrophy by modulating the VEGFR-2 signaling pathway.
Background Liver kinase B1 (LKB1) is a newly discovered tumor suppressor gene that plays a role in apoptosis induction. However, the precise impact of LKB1 expression on gastric cancer (GC) progression and its correlation with survivin and p53 in GC have not yet been elucidated. Purpose The aim of this study was to explore the significance of LKB1 expression and its correlation with p53 and survivin in GC. Patients and methods In this study, LKB1 expression was detected in GC and adjacent paracancerous tissues from 150 patients through immunohistochemical (IHC) staining. The relationship between LKB1 expression and clinical pathological factors in GC was analyzed, alongside its correlation with p53 and survivin expression. Results LKB1 expression was reduced in GC tissues compared with adjacent paracancerous tissues ( P =0.001). In patients with GC, lower LKB1 expression was associated with greater invasion depth ( P =0.013), higher pTNM stage ( P =0.009), and lymph node metastasis ( P =0.029). Furthermore, LKB1 expression in GC was inversely associated with p53 ( r =−0.181, P =0.027) and survivin expression ( r =−0.198, P =0.015). Kaplan–Meier analysis indicated that the expression of LKB1, p53 and survivin, as well as tumor differentiation, invasion, and pTNM and lymph node metastasis were all associated with overall survival (OS) (all P <0.05). Finally, multivariate analysis showed that LKB1 expression [hazard ratio (HR): 0.605 (0.414–0.882), P =0.009], p53 expression [hazard ratio (HR): 1.840 (1.232–2.750), P =0.003], and survivin expression [hazard ratio (HR): 1.561 (1.039–2.345), P =0.032] were all independent prognostic factors for patients with GC. Conclusion Our study suggests that LKB1 expression is reduced in GC, negatively correlated with p53 and survivin expression, and plays an important role in predicting invasion and metastasis of GC.
Background: Suxiao Xintong dropping pills (SXXTDP), a traditional Chinese medicine, is widely applied for treating myocardial infarction (MI). However, its therapy mechanisms are still unclear. Therefore, this research is designed to explore the molecular mechanisms of SXXTDP in treating MI. Methods: The active ingredients of SXXTDP and their corresponding genes of the active ingredients were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. MI-related genes were identified via analyzing the expression profiling data (accession number: GSE97320). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to study the shared genes of drug and disease. Through protein-protein interaction (PPI) network and the Cytoscape plugin cytoHubba, the hub genes were screened out. The compounds and hub targets binding were simulated through molecular docking method. Results: We obtained 21 active compounds and 253 corresponding target genes from TCMSP database. 1833 MI-related genes were identified according to P<0.05 and |log2FC| ≥ 0.5. 27 overlapping genes between drug and disease were acquired. GO analysis indicated that overlapping genes were mainly enriched in MAP kinase activity and antioxidant activity. KEGG analysis indicated that overlapping genes were mainly enriched in IL-17 signaling pathway and TNF signaling pathway. We obtained 10 hub genes via cytoHubba plugin. Six of the 10 hub genes, including PTGS2, MAPK14, MMP9, MAPK1, NFKBIA, and CASP8, were acted on molecular docking verification with their corresponding compounds of SXXTDP. Conclusion: SXXTDP may exert cardioprotection effect through regulating multiple targets and multiple pathways in MI.
Our results indicated that a higher 24-h BPV was associated independently with decreased endothelial-dependent and endothelial-independent vasodilator functions in a middle-aged normotensive population. Although 24-h BPV was associated with vasodilator function, relationships were attenuated after adjusting for covariates.
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