Long noncoding RNA SOX2OT is associated with myocardial fibrosis (MF) in heart failure (HF). This article aims to investigate the role of SOX2OT in MF. We constructed HF mouse models by subcutaneous injection of isoprenaline (ISO). Cardiac fibroblasts (CFs) were treated with ISO to induce MF. Hematoxylin-eosin, Masson, and Sirius-red staining were used to identify myocardial injury and collagen deposition in heart tissues. The relationship among SOX2OT, miR-138-5p, TGF-β1, and Smad3 were evaluated by chromatin immunoprecipitation and luciferase reporter assay. The gene and protein expression were verified by quantitative real-time PCR and western blot. We found that SOX2OT was up-regulated in HF mice and ISO-induced CFs. SOX2OT knockdown reduced myocardial injury and collagen deposition in HF mice. The expression of collagen I, α-SMA, TGF-β1, and p-Smad3 were inhibited by SOX2OT down-regulation in HF mice and ISO-induced CFs. Furthermore, TGF-β1 was a target gene of miR-138-5p and indirectly regulated by SOX2OT. SOX2OT promoted MF in HF by activating TGF-β1/Smad3, and then Smad3 interacted with the SOX2OT promoter and formed a positive feedback loop. In conclusion, our work verifies that SOX2OT/Smad3 feedback loop promotes MF in HF. Thus, SOX2OT is potentially a novel therapeutic target for MF in HF.
Background Identification of accurate prognostic biomarkers is still particularly urgent for improving the poor survival of lung cancer patients. In this study, we aimed to identity the potential biomarkers in Chinese lung cancer population via bioinformatics analysis. Methods In this study, the differentially expressed genes (DEGs) in lung cancer were identified using six datasets from Gene Expression Omnibus (GEO) database. Subsequently, enrichment analysis was conducted to evaluate the underlying molecular mechanisms involved in progression of lung cancer. Protein-protein interaction (PPI) and CytoHubba analysis were performed to determine the hub genes. The GEPIA, Human Protein Atlas (HPA), Kaplan-Meier plotter, and TIMER databases were used to explore the hub genes. The receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic value of hub genes. Reverse transcription quantitative PCR (qRT-PCR) was used to validate the expression levels of hub genes in 10 pairs of lung cancer paired tissues. Results A total of 499 overlapping DEGs (160 upregulated and 339 downregulated genes) were identified in the microarray datasets. DEGs were mainly associated with pathways in cancer, focal adhesion, and protein digestion and absorption. There were nine hub genes (CDKN3, MKI67, CEP55, SPAG5, AURKA, TOP2A, UBE2C, CHEK1 and BIRC5) identified by PPI and module analysis. In GEPIA database, the expression levels of these genes in lung cancer tissues were significantly upregulated compared with normal lung tissues. The results of prognostic analysis showed that relatively higher expression of hub genes was associated with poor prognosis of lung cancer. In HPA database, most hub genes were highly expressed in lung cancer tissues. The hub genes have good diagnostic efficiency in lung cancer and normal tissues. The expression of any hub gene was associated with the infiltration of at least two immune cells. qRT-PCR confirmed that the expression level of CDKN3, MKI67, CEP55, SPAG5, AURKA, TOP2A were highly expressed in lung cancer tissues. Conclusions The hub genes and functional pathways identified in this study may contribute to understand the molecular mechanisms of lung cancer. Our findings may provide new therapeutic targets for lung cancer patients.
This research was aimed at exploring the changes in right ventricular function in patients after the recovery of coronavirus disease 2019 (COVID-19) under echocardiography and providing a reference for the rehabilitation and treatment of COVID-19 patients. Three echocardiographic follow-up examinations were performed on 40 recovered COVID-19 patients and 40 healthy people. Right ventricular function between patients after COVID-19 rehabilitation and healthy people was compared. The mean values of right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), right ventricular ejection fraction (RVEF), right myocardial performance index (RMPI), and tricuspid annular plane systolic speed (S’) were compared between patients after COVID-19 rehabilitation and healthy subjects. The technical parameters of two-dimensional speckle tracking were compared. The results showed that the differences in RVFAC, TAPSE, RVEF, and RMPI between COVID-19 patients and healthy controls were not significant during the three follow-up periods ( P > 0.05 ). At the first follow-up, the S’ was 12.78 cm/s in COVID-19 patients and 13.18 cm/s in healthy subjects. At the second follow-up, the S’ was 11.98 cm/s in COVID-19 patients and 12.77 cm/s in healthy subjects. At the third follow-up, the S’ was 12.79 cm/s in COVID-19 patients and 13.12 cm/s in healthy subjects. There was no significant difference between the two groups ( P > 0.05 ). In addition, there was no significant difference in right ventricular function between COVID-19 patients and healthy controls, and there was no significant difference in cardiovascular symptoms ( P > 0.05 ). In summary, COVID-19 had no substantial effect on right ventricular function and better recovery in patients.
Background and Aims:The goal of this study was to investigate the mechanism by which the long noncoding RNA MALAT1 inhibited hepatocyte proliferation in acute liver injury (ALI). Methods: Lipopolysaccharide (LPS) was used to induce an ALI cellular model in HL7702 cells, in which lentivirus vectors containing MALAT1/EZH2/GFER overexpression or knockdown were introduced. A series of experiments were performed to determine their roles in liver injury, oxidative stress injury, and cell biological processes. The interaction of MALAT1 with EZH2 and enrichment of EZH2 and H3K27me3 in the GFER promoter region were identified. Rats were treated with MALAT1 knockdown or GFER overexpression before LPS induction to verify the results derived from the in vitro assay. Results: MALAT1 levels were elevated and GFER levels were reduced in ALI patients and the LPS-induced cell model. MALAT1 knockdown or GFER overexpression suppressed cell apoptosis and oxidative stress injury induced cell proliferation, and reduced ALI. Functionally, MALAT1 interacted directly with EZH2 and increased the enrichment of EZH2 and H3K27me3 in the GFER promoter region to reduce GFER expression. Moreover, MALAT1/EZH2/GFER was activated the AMPK/mTOR signaling pathway. Conclusion: Our study highlighted the inhibitory role of reduced MALAT1 in ALI through the modulation of EZH2-mediated GFER.
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