Senescence is a result of cellular stress and is a potential mechanism for regulating cancer. As a member of the mitogen-activated protein kinase family, ERK1/2 (extracellular signal-regulated protein kinase) has an important role in delivering extracellular signals to the nucleus, and these signals regulate the cell cycle, cell proliferation and cell development. Previous studies demonstrated that ERK1/2 is closely associated with cell aging; however other previous studies suggested that ERK1/2 exerts an opposite effect on aging models and target proteins, even within the same cell model. Recent studies demonstrated that the effect of ERK1/2 on aging is likely associated with its target proteins and regulators, negative feedback loops, phosphorylated ERK1/2 factors and ERK1/2 translocation from the cytoplasm to the nucleus. The present review aims to examine the mechanism of ERK1/2 and discuss its role in cellular outcomes and novel drug development.
Glioma is the most aggressive and malignant type of primary intracranial tumor. In recent decades, despite the rapid development of modern surgery and therapeutic strategies available for brain tumors, the prognosis of glioma remains poor and the median survival time is <15 months. In this study, we found that the levels of miRNA-320a were significantly decreased in patients with glioma, and that elevated miRNA-320a expression was associated with a better prognosis. In addition, aquaporin 4 (AQP4) was identified as a direct target of miRNA-320a. Overexpression of miRNA-320a led to the inhibition of cell invasion and migration via targeting of AQP4. Therefore, our results suggested that miRNA-320a could suppress the aggressive capacity of tumors by targeting AQP4, and that miRNA-320a could serve as a new effective therapeutic target for glioma surgical and therapeutic strategies.
20(S)-ginsenoside Rh2 [(S)Rh2] possesses potential to prevent cancer in vitro as well as in vivo, but the underlying mechanism is still unknown. First, we infected HepG2 cells with lentivirus which carries β‑catenin. We detected the pharmacological effects of (S)Rh2 on HepG2 and HepG2‑β‑catenin cells and found that the IC50 of (S)Rh2 exposure on HepG2-β-catenin cells was higher than HepG2 cells. Flow cytometry (FCM) indicated that (S)Rh2 could be arrested in G0/G1 phase and induce early apoptosis in HepG2 and HepG2‑β‑catenin cells. Second, ELISA kit was used to check the activity of glycogen synthase kinase‑3β (GSK‑3β), which was upregulated by (S)Rh2. GSK‑3β inhibitor BIO, was used to verify that (S)Rh2 activated GSK‑3β. PCR and western blotting results indicated that (S)Rh2 could degrade the expression of β‑catenin, which combined with TCF in the nucleus and activate transcription of Wnt target genes, such as Bax, Bcl‑2, cyclin D1, MMP3, which were checked by chromatin immunoprecipitation (ChIP), PCR and western blotting. The results showed that the expression of Bax mRNA and proteins increased, while the cyclin D1, Bcl‑2, MMP3 mRNA and proteins were downregulated in HepG2 and HepG2‑β‑catenin cells which was induced by (S)Rh2. By contrast, with the HepG2-β-catenin + (S)Rh2 group, the expression of other mRNA and proteins in HepG2 + (S)Rh2 group changed significantly. In vivo, experiments were performed using a nude mouse xenograft model to investigate the (S)Rh2 effect. So these results suggested that (S)Rh2 could suppress proliferation, promote apoptosis and inhibit metastasis of HepG2, decrease weight of tumor by downregulating β‑catenin through activating GSK‑3β and the pharmacological effect of (S)Rh2 on HepG2 cells might be weakened by overexpression of β‑catenin.
BackgroundEpithelioid rhabdomyosarcoma is a rare tumor that generally occurs in the bladder, the parotid gland, or the skin of the neck. We describe an unusual case of primary epithelioid rhabdomyosarcoma of the stomach and review the literature.Case presentationA 64-year-old woman presented with a lesion at the gastroesophageal junction. Histopathological examination showed irregularly sized round cells with low cytoplasmic content and eccentric nuclei. Mitotic figures were present. Fibrovascular septa and areas of necrosis were observed between tumor cells. Tumor cells were strongly positive for MyoD1, desmin, and myogenin, and weakly positive for actin, CD56, and PGP9.5. The ki-67 index was ≥90%.ConclusionsPrimary epithelioid rhabdomyosarcoma of the stomach is extremely rare. Better awareness of this entity is necessary for early diagnosis and treatment.
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