Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase involved in cell proliferation, invasion, angiogenesis, and metastasis in various cancers, including hepatocellular carcinoma (HCC). However, the role and molecular mechanisms of EZH2 in HCC radiosensitivity remain unclear. Here, we show that EZH2 is upregulated in HCC cells and the aberrantly overexpressed EZH2 is associated with the poor prognosis of HCC patients. Using miRNA databases, we identified miR-138-5p as a regulator of EZH2. We also found that miR-138-5p was suppressed by EZH2-induced H3K27me3 in HCC cell lines. MiR-138-5p overexpression and EZH2 knockdown enhanced cellular radiosensitivity while inhibiting cell migration, invasion, and epithelial-mesenchymal transition (EMT). Analysis of RNA-seq datasets revealed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway was the main enrichment pathway for differential genes after miR-138-5p overexpression or EZH2 knockdown. Expression level of HIF-1α was significantly suppressed after miR-138-5p overexpression or silencing of EZH2. HIF-1α silencing mitigated resistance of HCC cells and inhibited EMT. This study establishes the EZH2/miR-138-5p/HIF-1α as a potential therapeutic target for sensitizing HCC to radiotherapy.
Morphol., 34(1):197-204, 2016.
SUMMARY:The aim of this study was to investigate the course of the supraorbital nerve and temporal branch of the facial nerve, and to verify the clinical security of cutting the frontalis muscle flap to treat blepharoptosis in one-third of the eyebrow. Twenty cadavers were dissected. The relationship of the supraorbital nerve and the course of the frontotemporal branch of the facial nerve with the head and neck muscles was evaluated. Forty patients underwent clinical frontal muscular flap suspension surgery for the treatment of blepharoptosis. The postoperative curative and complication rates were determined. The courses of the supraorbital nerve and frontotemporal branch of the facial nerve were observed to determine a relatively safe area in one-third of the eyebrow. The average width of the zone was 25.0±3.5 mm. In forty cases, satisfactory results were achieved in correcting blepharoptosis by cutting the frontal muscular flap in the middle of eyebrow within the wide range of 17±2.1 mm. No secondary sensory and motor dysfunctions occurred. One-third of the eyebrow (eyebrow center, within 17±2.1 mm) was a relatively safe area and allowed for the prevention of damage to the temporal branch of the facial nerve inside the supraorbital nerve and supraorbital artery and the outer frontotemporal branch of the facial nerve.
Background Carbon tetrachloride (CCL4) is highly toxic to animal liver and is a major factor leading to liver injury. Gomphrena globosa L. (GgL) is a comestible plant with anti-inflammation and antioxidation properties. This study was aim to investigate the potential therapeutic effects of GgL on liver injury. Methods and Results A mice model of chronic liver injury was established by intraperitoneal injection of CCl4 (0.4 mL/kg) for 3 weeks, and the mice were treated intraperitoneally with different concentrations of GgL crude extract (GgCE; 100, 200, 300 mg/kg) or Bifendatatum (Bif; 20 mg/kg) in the last 2 weeks. The results showed that GgCE treatment could alleviate the liver injury induced by CCL4, improve the pathological changes caused by CCL4 on the mice liver, and enhance the antioxidant capacity. We also found that GgCE increased the expression of antioxidant stress related proteins, decreased the phosphorylation levels of autophagy related proteins PI3K and mTOR, and decreased the expression of LC3 Ⅱ and P62 proteins. Conclusions These results suggest that GgCE alleviated CCL4-induced chronic liver injury in mice by activating antioxidant signaling pathways and promoting autophagy, indicating a potential therapeutic effect of GgCE on liver injury.
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