No abstract

Worldwide, breast cancer is the most frequently diagnosed life-threatening cancer in women and is the leading cause of cancer-related mortality among women. It is extremely rare but highly lethal in men. The deubiquitinating enzyme USP39 plays important roles in mRNA processing, and our previous data showed that high levels of USP39 are selectively present in different types of human breast tumor cells. The potential of USP39 as a therapeutic target for breast cancer was investigated. The expression levels of USP39 protein in 23 breast cancer specimens were quantified using an immunohistochemical assay and were found to have high levels in human breast cancer tissues when compared to these levels in normal breast tissues. In the breast cancer cell line MCF-7, USP39 expression was knocked down by a lentiviral short hairpin RNA (shRNA) delivery system. The RNA interference (RNAi)-mediated downregulation of USP39 expression markedly reduced the proliferative and colony forming ability of MCF-7 cells. In addition, the inhibition of USP39 induced G0/G1-phase arrest and apoptosis of the cells. These results suggest that USP39 may act as an oncogenic factor in breast cancer and could be a potential molecular target for breast cancer gene therapy.

A nanohybrid based on nanoscale graphene oxide (NGO) and dextran has been designed and employed for effectively killing drug-resistant MCF-7/ADR cells. This graphene-based nanohybrid was readily prepared through π-π interaction of NGO and hematin-terminated dextran (HDex), being denoted as NGO-HDex. It revealed an improved stability in physiological conditions as compared to native NGO. Besides, NGO-HDex could efficiently load doxorubicin (DOX), an anticancer drug, with drug loading capacity of 3.4 mg/mg NGO and liberate the drug with a pH-dependent profile. Cell viability assay indicated that the NGO-HDex displayed lower cytotoxicity against MCF-7/ADR cells as compared to native NGO. DOX-loaded NGO-HDex, however, revealed more efficient killing effect in the cells than free DOX because the nanohybrid caused a higher amount of DOX accumulated in the cells. The results of this study highlight that the NGO-HDex has high potential for killing drug-resistant cancer cells.

No abstract

The altered expression of miRNAs is involved in carcinogenesis of esophageal squamous cell carcinoma (ESCC), but whether miRNAs regulate COX-2 expression in ESCC is not clear. To this end, the expression levels of miR-26a and miR-144 in ESCC clinical tissues and cell lines were investigated by qRT-PCR. COX-2 and PEG2 were quantified by western blot and ELISA. Decrease in miR-26a and miR-144 expression in ESCC was found by a comparison between 30 pairs of ESCC tumor and adjacent normal tissues as well as in 11 ESCC cell lines (P < 0.001). Co-transfection of miR-26a and miR-144 in ESCC cell lines more significantly suppressed cell proliferation, migration, and invasion than did either miR-26a or miR-144 alone (all P < 0.001), as shown by assays of CCK8, migration and invasion and flow cytometry. The inhibitory effect of these two miRNAs in vivo was also verified in nude mice xenograft models. COX-2 was confirmed as a target of miR-26a and miR-144. In conclusion, miR-26a and miR-144 expression is downregulated in ESCC. Co-expression of miR-26a and miR-144 in ESCC cells resulted in inhibition of proliferation and metastasis in vitro and in vivo, suggesting that targeting COX-2 may be the mechanism of these two miRNAs.