Human Cell最新文献

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Dysregulation of long non-coding RNAs (lncRNAs) plays crucial roles in the initiation and progression of TNBC. In this study, we analyzed public GEO profiles to verify the key lncRNAs in TNBC. Linc00921 was selected for further study. Low expression of linc00921 was observed in 49 of 95 TNBC tissues. Low expression of linc00921 was correlated with poor postoperative disease-free survival (DFS) and overall survival (OS) of TNBC patients. Overexpression of linc00921 with lentivirus suppressed the proliferation, migration and invasion of TNBC cells. A luciferase reporter assay showed that linc00921 could sponge miR-9-5p in TNBC. Moreover, linc00921 and miR-9-5p occupied the same Argonaute-2 (Ago2) protein in TNBC cells. Leucine zipper tumor suppressor 2 (LZTS2) was recognized as a target gene of miR-9-5p, and thereby a linc00921/miR-9-5p/LZTS2 axis was identified in TNBC cells. Overexpression of linc00921 promoted nuclear export of β-catenin, neutralized its function, and subsequently promoted epithelial-to-mesenchymal transition (EMT) in TNBC. A xenograft tumor mouse model showed that the miR-9-5p inhibitor upregulates LZTS2 expression and induce nuclear export of β-catenin in TNBC. Thus, linc00921 upregulates LZTS2 by sponging miR-9-5p to suppress tumorigenesis and EMT of TNBC. Linc00921/miR-9-5p/LZTS2 axis may be a novel biomarker and therapeutic target for TNBC patients.

Periodontitis is the leading cause of tooth loss, and patients with smoking habits are at an increased risk of developing periodontitis. A20 (the tumor necrosis factor alpha-induced protein 3, TNFAIP3) is one of the key regulators of inflammation and cell death in numerous tissues. Emerging researches indicated A20 as a fundamental molecule in the periodontal tissue. This study was to evaluate the role of A20 against cell death and inflammation in periodontitis and to elucidate the underlying mechanisms. In our study, western blot, autophagy detection, and transmission electron microscopy showed that lipopolysaccharide from Porphyromonas gingivalis (Pg.LPS) and nicotine (NI) could enhance the activation of autophagy. Pg.LPS and NI induce the pyroptosis of human periodontal ligament cells (hPDLCs), as evidenced by the decrease of membrane integrity and the increase of NLRP3, GSDMD, GSDMD-N, caspase-1 activity, and the pro-inflammatory cytokines of IL-1β, IL-6, TNF-α. Further researches were focused on that A20, an ubiquitin-editing enzyme, was linked to hPDLCs pyroptosis. Overexpression or silencing A20 could diminish or aggravate pyroptosis in hPDLCs by the modulation of autophagy. The above results demonstrated that A20 dictated the cross-talk between pyroptosis and autophagy. Overexpression of A20 enhanced autophagy to reduce pyroptosis, and thus alleviating inflammation, suggesting that A20 may be a potent target in the treatment of periodontitis.

Autophagy suppression plays key a role during myocardial fibrosis (MF) progression. Exosomes from stem cells attenuate MF. The current study aimed to explain the antifibrosis effects of exosomes by focusing on microRNAs (miRs). MF was induced in rats using transverse aortic constriction (TAC) method and handled with exosomes from bone mesenchymal stem cells (BMSCs). The results of in vivo assays were verified with H9c2 cells. MiR expression profile was determined using microarray detection. The influence of miR-199a-3p modulation in vivo and in vitro on the antifibrosis effect of exosomes then was assessed. Exosomes attenuated MF by inhibiting inflammation, improving tissue structure, and inhibiting fibrosis-related indicators in TAC rats, and the effects were associated with autophagy activation. In H9c2 cells, exosomes suppressed cell viability, induced cell apoptosis, inhibited fibrosis-related indicators, while and the inhibition of autophagy by 3-MA would block the effect of exosomes. Based on the microarray detection, miR-199a-3p level was selected as therapeutic target. The inhibition of miR-199a-3p impaired the antifibrosis effects of exosomes on H9c2 cells, which was associated with autophagy inhibition. Collectively, exosomes from BMSCs exerted antifibrosis effects via the distant transfer of miR-199a-3p to heart tissues, which induced autophagy by inhibiting mTOR.

Mechanical ventilation may cause ventilator-induced lung injury (VILI) in patients requiring ventilator support. Inhibition of autophagy is an important approach to ameliorate VILI as it always enhances lung injury after exposure to various stress agents. This study aimed to further reveal the potential mechanisms underlying the effects of geranylgeranyl diphosphate synthase large subunit 1 (GGPPS1) knockout and autophagy in VILI using C57BL/6 mice with lung-specific GGPPS1 knockout that were subjected to mechanical ventilation. The results demonstrate that GGPPS1 knockout mice exhibit significantly attenuated VILI based on the histologic score, the lung wet-to-dry ratio, total protein levels, neutrophils in bronchoalveolar lavage fluid, and reduced levels of inflammatory cytokines. Importantly, the expression levels of autophagy markers were obviously decreased in GGPPS1 knockout mice compared with wild-type mice. The inhibitory effects of GGPPS1 knockout on autophagy were further confirmed by measuring the ultrastructural change of lung tissues under transmission electron microscopy. In addition, knockdown of GGPPS1 in RAW264.7 cells reduced cyclic stretch-induced inflammation and autophagy. The benefits of GGPPS1 knockout for VILI can be partially eliminated through treatment with rapamycin. Further analysis revealed that Rab37 was significantly downregulated in GGPPS1 knockout mice after mechanical ventilation, while it was highly expressed in the control group. Simultaneously, Rab37 overexpression significantly enhances autophagy in cells that are treated with cyclin stretch, including GGPPS1 knockout cells. Collectively, our results indicate that GGPPS1 knockout results in reduced expression of Rab37 proteins, further restraining autophagy and VILI.