Hormetic and adaptive responses induced by low-level radiation in hematopoietic and immune systems have been observed, as shown by stimulatory effects on cell growth and resistance to subsequent radiation-induced cytogenetic damage. However, in terms of cell death by apoptosis, the effects of low-level radiation are controversial: Some studies showed decreased apoptosis in response to low-level radiation while others showed increased apoptosis. This controversy may be related to the radiation doses or dose rates and also, more importantly, to the cell types. Testes are one of the most radiosensitive organs. The loss of male germ cells after exposure to ionizing radiation has been attributed to apoptosis. In the present study, the effects of low-level radiation at doses up to 200 mGy on mouse male germ cells in terms of apoptosis and the expression of apoptosis-related proteins were examined at different times after whole-body exposure of mice to low-level radiation. In addition, the effect of pre-exposure to low-level radiation on subsequent cell death induced by high doses of radiation was examined to explore the possibility of low-level radiation-induced adaptive response. The results showed that low-level radiation in the dose range of 25-200 mGy induced significant increases in apoptosis in both spermatogonia and spermatocytes, with the maximal effect at 75 mGy. The increased apoptosis is most likely associated with Trp53 protein expression. Furthermore, 75 mGy low-level radiation given pre-irradiation led to an adaptive response of seminiferous germ cells to subsequent high-level radiation-induced apoptosis. These results suggest that low-level radiation induces increased apoptosis in male germ cells but also induces a significant adaptive response that decreases cell death after a subsequent high-dose irradiation.

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MicroRNAs (miRNAs) are important regulators of multiple cellular processes, and the deregulation of miRNA is a common event in diverse human diseases, particularly cancer. However, the mechanisms underlying the relationship between disordered miRNA expression and tumorigenesis have remained largely unknown. In this study, we demonstrated the down-regulation of miR-125b in hepatocellular carcinoma (HCC) tissues and HCC cell lines by Northern blot and quantitative RT-PCR analyses. The ectopic expression of miR-125b reduced the cellular proliferation and cell cycle progression of HCC cells by targeting Mcl-1 and IL6R. Furthermore, the miR-125b-induced inhibition of cell proliferation was rescued by the expression of Mcl-1 or IL6R variants that lacked 3′ UTRs. Thus, this study revealed the differential expression of miR-125b in HCC cells and elucidated its potential as a tumor suppressor in HCC development.

BackgroundMicroRNAs act as posttranscriptional regulators of gene expression in many biological processes. Their deregulations occur commonly in gastric cancer (GC). Although DNA methylation constitutes an important mechanism for microRNA deregulation in cancer, this field largely remains unexplored.Methodology/Principal FindingsTotal RNA was extracted from the tissues of 100 patients with GC and four gastric cancer cell lines. The expression levels of miR-10a were determined by real-time PCR with specific TaqMan probes. Moreover, a functional analysis of miR-10a in regulating cell proliferation, migration and invasion was performed. Subsequently, quantitative methylation-specific PCR (qMSP) was used to detect the DNA methylation status in the CpG islands upstream of miR-10a. In this study, we found that the expression of miR-10a in GC cells was lower than that in normal cells, which was due to the hypermethylation of the CpG islands upstream of miR-10a. We also validated the slightly lower expression of miR-10a in GC tissues than their adjacent non-neoplastic tissues in 100 GC patients and confirmed the hypermethylation of CpG islands upstream of miR-10a in some patients. Furthermore, re-introduction of miR-10a into GC cells was able to inhibit cell proliferation, migration and invasion. Bioinformatic and immunoblot analysis indicated that the tumor suppressor roles of miR-10a in GC cells were possibly through targeting HOXA1.Conclusions/SignificanceOur data indicate that miR-10a acts as a tumor suppressor in GC cells and is partially silenced by DNA hypermethylation in GC, suggesting that miR-10a may serve as a potential diagnostic or therapeutic target of GC.

A growing body of evidence suggests that microRNA-365 (miR-365) played crucial role in the initiation and development of many types of cancers. However, the biological role of miR-365 in human glioma remains unclear. Herein, the aims of this study were to investigate the role and underlying mechanisms of miR-365 in glioma by a series of in vitro and in vivo experiments. We found that miR-365 was strongly downregulated in malignant glioma tissues and cell lines. Restoration of the expression of miR-365 in glioma cells significantly inhibited cell proliferation, migration and invasion in vitro and tumor growth in vivo. Notably, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was proved to be a direct target of miR-365 in glioma cells, and its mRNA expression was inversely correlated with miR-365 expression in clinical glioma tissues. PIK3R3 overexpression in miR-365 expressing cells could rescue proliferation, migration and invasion inhibition of miR-365. In addition, miR-365 was able to inhibit the phosphorylation of AKT and mTOR in vitro and in vivo, which are key participants in the AKT/mTOR pathway. These results suggest that miR-365 functioned as a tumor suppressor in glioma by targeting PIK3R3, suggesting that miR-365 has potential as therapeutic targets for glioma.

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Overall, these results demonstrate that exposure to heat stress can improve the immunogenicity of exosomes obtained from malignant ascites of gastric cancer patients.

MicroRNA is strongly associated with tumor growth and development. This study examined the potential roles of miR-125b in glioma growth. We found that miR-125b promotes glioma cell line growth and clone formation, and protects the glioma cells from apoptosis in vitro. The miR-125b-transfected glioma cells also demonstrated increased growth after in vivo transplantation. We further identified that miR-125b inhibits Connexin43 expression, and the overexpression of Connexin43 antagonizes the effects of miR-125b in cell growth and anti-apoptosis. We conclude that miR-125b regulates glioma growth partly through Connexin43 protein.