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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.

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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.

Background and Purpose In non‐small‐cell lung carcinoma (NSCLC) patients, the L858R/T790M mutation of the epithelial growth factor receptor (EGFR) is a major cause of acquired resistance to EGFR‐TKIs treatment that limits their therapeutic efficacy. Identification of drugs that can preferentially kill the NSCLC harbouring L858R/T790M mutation is therefore critical. Here, we have evaluated the effects of ursolic acid, an active component isolated from herbal sources, on erlotinib‐resistant H1975 cells that harbour the L858R/T790M mutation. Experimental Approach Gene expression omnibus (GEO) profiles analyses was applied to detect differentially expressed genes in NSCLC cells harbouring EGFR mutation. AnnexinV‐FITC/PI, TUNEL staining, MTT, wound healing, RT‐PCR, qRT‐PCR, western blots, immunostaining, dual‐luciferase reporters and ChIP‐PCR were utilized to investigate the effects of ursolic acid in vitro and in vivo. Key Results The cancer/testis antigen family 45 member A2 (CT45A2) was highly expressed in H1975 cells. Ectopic expression of CT45A2 in H1975 cells increased cell proliferation and motility in vitro. Silencing the CT45A2 expression strongly attenuated H1975 cells motility and growth. The anti‐cancer effect of ursolic acid was critically dependent on CT45A2 expression in H1975 cells. Ursolic acid suppressed CT45A2 gene transcription mediated by transcriptional factor TCF4 and β‐catenin signalling. Conclusions and Implications CT45A2 is a novel oncogene for NSCLC with an EGFR T790 mutation. Ursolic acid induced apoptosis and inhibited proliferation of H1975 cells by negatively regulating the β‐catenin/TCF4/CT45A2 signalling pathway. Therefore, ursolic acid may be a potential candidate treatment for NSCLC harbouring the EGFR‐L858R/T790M mutation.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively triggers cancer cell death via its association with death receptors on the cell membrane, but exerts negligible side effects on normal cells. However, some non-small-cell lung carcinoma (NSCLC) patients exhibited resistance to TRAIL treatment in clinical trials, and the mechanism varies. In this study, we described for the first time that toosendanin (TSN), a triterpenoid derivative used in Chinese medicine for pain management, could significantly sensitize human primary NSCLC cells or NSCLC cell lines to TRAIL-mediated apoptosis both in vitro and in vivo, while showing low toxicity against human primary cells or tissues. The underlying apoptotic mechanisms involved upregulation of death receptor 5 (DR5) and CCAAT/enhancer binding protein homologous protein, which is related to the endoplasmic reticulum stress response, and is further associated with reactive oxygen species generation and Ca2+ accumulation. Surprisingly, TSN also induced autophagy in NSCLC cells, which recruited membrane DR5, and subsequently antagonized the apoptosis-sensitizing effect of TSN. Taken together, TSN can be used to sensitize tumors and the combination of TRAIL and TSN may represent a useful strategy for NSCLC therapy; moreover, autophagy serves as an important drug resistance mechanism for TSN.

This 1:5 case‐control study aimed to identify the risk factors of hospital‐acquired pressure injuries (HAPIs) and to develop a mathematical model of nomogram for the risk prediction of HAPIs. Data for 370 patients with HAPIs and 1971 patients without HAPIs were extracted from the adverse events and the electronic medical systems. They were randomly divided into two sets: training (n = 1951) and validation (n = 390). Significant risk factors were identified by univariate and multivariate analyses in the training set, followed by a nomogram constructed. Age, independent movement, sensory perception and response, moisture, perfusion, use of medical devices, compulsive position, hypoalbuminaemia, an existing pressure injury or scarring from a previous pressure injury, and surgery sufferings were considered significant risk factors and were included to construct a nomogram. In both of the training and validation sets, the areas of 0.90 under the receiver operating characteristic curves showed excellent discrimination of the nomogram; calibration plots demonstrated a good consistency between the observed probability and the nomogram's prediction; decision curve analyses exhibited preferable net benefit along with the threshold probability in the nomogram. The excellent performance of the nomogram makes it a convenient and reliable tool for the risk prediction of HAPIs.