No abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumours and it carries a poor prognosis due to a high rate of recurrence or metastasis after surgery. Bmi-1 plays a significant role in the growth and metastasis of many solid tumours. However, the exact mechanisms underlying Bmi-1-mediated cell invasion and metastasis, especially in HCC, are not yet known. In the present study, we sought to evaluate the expression of Bmi-1 in HCC samples and its relationship with clinicopathological characteristics and prognostic value, we also investigated related mechanisms underlying Bmi-1-mediated cell invasion in HCC. Our results showed that Bmi-1 is upregulated in HCC tissues compared to matched non-cancer liver tissues; and its expression is positively associated with tumour size, metastasis, venous invasion and AJCC TNM stage, respectively; multivariate analysis showed that high expression of Bmi-1 was an independent prognostic factor for overall survival. In addition, the shRNA-mediated inhibition of Bmi-1 reduced the invasiveness of two HCC cell lines in vitro by upregulating phosphatase and the tensin homolog deleted on chromosome 10 (PTEN) expression, inhibiting the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway and downregulating the expression and activities of matrix metalloproteinase (MMP)-2 and MMP-9 and vascular endothelial growth factor (VEGF). These data demonstrate that Bmi-1 plays a vital role in HCC invasion and that Bmi-1 is a potential therapeutic target for HCC.

An increasing body of evidence indicates that inflammation and apoptosis are involved in the development of acute myocardial infarction (AMI). In this study, we sought to investigate the specific role and the underlying regulatory mechanism of miR-145-5p in myocardial ischemic injury. H9c2 cardiac cells were exposed to hypoxia to establish a model of myocardial hypoxic/ischemic injury. We found that miR-145-5p was notably down-regulated, while CD40 expression was highly elevated in H9c2 cells following exposure to acute hypoxia. Additionally, hypoxia markedly enhanced the inflammatory response, as reflected by an increase in the secretion of the cytokines IL-1β, TNF-α, and IL-6, whereas the introduction of miR-145-5p effectively suppressed inflammatory factor production triggered by hypoxia. Furthermore, we observed hypoxia stimulation significantly augmented apoptosis accompanied by a decrease in the expression of Bcl-2 and an increase in the expression of Bax, Caspase-3, and Caspase-9. However, augmentation of miR-145-5p led to a dramatic prevention of hypoxia-induced apoptosis. Importantly, we identified CD40 as a direct target of miR-145-5p. Interestingly, the depletion of CD40 with small interfering RNAs (siRNAs) apparently repressed the production of inflammatory cytokines and apoptosis in the setting of acute hypoxic treated. Taken together, these data demonstrated that miR-145-5p may function as a cardiac-protective molecule in myocardial ischemic injury by ameliorating inflammation and apoptosis via negative regulation of CD40. The study gives evidence that miR-145-5p provides an interesting strategy for protecting cardiomyocytes from hypoxia-induced inflammatory response and apoptosis.