miR­92a contributes to cell proliferation, apoptosis and doxorubicin chemosensitivity in gastric carcinoma cells.

MicroRNAs (miRNAs) are a class of short noncoding RNAs that negatively regulate gene expression and act as oncogenes or tumor suppressors. Numerous miRNAs have been reported be associated with the occurrence and development of gastric carcinoma (GC). For instance, miR­92a has been observed to be overexpressed in GC; however, the precise mechanisms underlying the role of miR­92a in GC and its role in clinical therapy require further investigation. In the present study, it was reported that miR­92a expression was significantly upregulated in GC tissues compared with in adjacent tissues. Additionally, suppression of miR­92a significantly reduced SGC7901 cell viability as demonstrated by a Cell Counting Kit­8 and colony formation assays. Suppression of miR­92a inhibited SGC7901 cell proliferation as determined by Ki­67 immunofluorescence staining, and the expression levels of proliferating cell nuclear antigen, cyclin dependent kinase (CDK)4 and CDK6, and increased that of p53. In addition, we reported that suppression of miR­92a induced apoptosis in SGC7901 cells. Furthermore, bioinformatics analysis identified that ING2 as a potential target of miR­92a. Downregulation of miR­92a significantly increased ING2 expression at the mRNA and protein levels. A dual­luciferase reporter assay validated a direct binding site of miR­92a on ING2. In addition, SGC7901 cells with suppression of miR­92a were more sensitive to doxorubicin treatment. Knockdown of miR­92a reduced the half­maximal inhibitory concentration of doxorubicin from 147.6 nM to 82.1 nM in SGC7901 cells. Knockdown of miR­92a also reduced SGC7901 cell survival under doxorubicin stimulation. Furthermore, SGC7901 cells with suppression of miR­92a harbored a greater number of DNA damage foci upon doxorubicin treatment compared with in control cells. The findings of the present study revealed that miR­92a contributes to cell proliferation, apoptosis and doxorubicin chemosensitivity in GC cells, which suggests a potential therapeutic strategy for the treatment of GC.

Endoplasmic reticulum stress mediates the arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells.

Arsenic trioxide has been proven to trigger apoptosis in human hepatocellular carcinoma cells. Endoplasmic reticulum stress has been known to be involved in apoptosis through the induction of CCAAT/enhancer-binding protein homologous protein. However, it is unknown whether endoplasmic reticulum stress mediates arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells. Our data showed that arsenic trioxide significantly induced apoptosis in human hepatocellular carcinoma cells. Furthermore, arsenic trioxide triggered endoplasmic reticulum stress, as indicated by endoplasmic reticulum dilation, upregulation of glucose-regulated protein 78 and CCAAT/enhancer-binding protein homologous protein. We further found that 4-phenylbutyric acid, an inhibitor of endoplasmic reticulum stress, alleviated arsenic trioxide-induced expression of CCAAT/enhancer-binding protein homologous protein. More important, knockdown of CCAAT/enhancer-binding protein homologous protein by siRNA or inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid alleviated apoptosis induced by arsenic trioxide. Consequently, our results suggested that arsenic trioxide could induce endoplasmic reticulum stress-mediated apoptosis in hepatocellular carcinoma cells, and that CCAAT/enhancer-binding protein homologous protein might play an important role in this process.