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Colorectal cancer (CRC) is a global public health issue with increasing prevalence. MicroRNA-934 (miR-934) is a kind of non-coding RNA involved in the regulation of diverse cancers. Though previous researches have revealed part of association between miR-934 and CRC, the role of miR-934 in CRC pathogenesis has not been completely explored yet. In this study, we aim to investigate the effect of miR-934 on cell proliferation, migration, invasion and angiogenesis in CRC. Accordingly, miR-934 was found to be over-expressed in SW480 and HCT116 cells, two typical CRC cell lines. Meanwhile, miR-934 knockdown significantly inhibited cell proliferation and induced cell cycle arrest in SW480 and HCT116 cells. It was further validated that miR-934 knockdown displayed an inhibitory effect on cell migration and invasion in SW480 and HCT116 cells. Additionally, miR-934 deficiency markedly decreased VEGF expression in SW480 and HCT116 cells and suppressed capability of CRC cells to promote tube formation in vascular endothelial cells, which suggests the pro-angiogenesis role of miR-934 in vitro. Dual luciferase reporter assay further showed that miR-934 directly bound to B-cell translocation gene 2 (BTG2). BTG2 knockdown reversed the inhibitory effect of miR-934 silencing on cell proliferation, migration, invasion, and angiogenesis in SW480 and HCT116 cells. In summary, this study suggests that miR-934 facilitates CRC progression by targeting BTG2, and further highlights the role of miR-934 in pathogenesis of CRC.

Subunit 6 of the COP9 signalosome complex, CSN6, is known to be critical to the regulation of the MDM2-p53 axis for cell proliferation and anti-apoptosis, but its many targets remain unclear. Here we show that p57Kip2 is a target of CSN6, and that CSN6 is a negative regulator of p57Kip2. CSN6 associates with p57Kip2, and its overexpression can decrease the steady-state expression of p57Kip2; accordingly, CSN6 deficiency leads to p57Kip2 stabilization. Mechanistic studies show that CSN6 associates with p57Kip2 and Skp2, a component of the E3 ligase, which, in turn, facilitates Skp2-mediated protein ubiquitination of p57Kip2. Loss of Skp2 compromised CSN6-mediated p57Kip2 destabilization, suggesting collaboration between Skp2 and CSN6 in degradation of p57Kip2. CSN6’s negative impact on p57Kip2 elevation translates into cell growth promotion, cell cycle deregulation and potentiated transformational activity. Significantly, univariate Kaplan-Meier analysis of tumor samples demonstrates that high CSN6 expression or low p57 expression is associated with poor overall survival. These data suggest that CSN6 is an important negative regulator of p57Kip2, and that overexpression of CSN6 in many types of cancer could lead to decreased expression of p57Kip2 and result in promoted cancer cell growth.

Background At present, few studies have explored the significance of POU5F1 (also known as octamer-bingding factor, Oct-4 or Oct-3) expression in breast cancer tissues. Methods A total of 121 patients were retrospectively selected between May 2010 and March 2013 to investigate the relationship between POU5F1/Oct-4 expression in breast cancer tissues and non-sentinel lymph node (non-SLN) metastases and to validate the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram. All patients had early-stage breast cancer, which was histologically confirmed by the Department of Surgical Oncology, The First Affiliated Hospital of China Medical University. Histological type and grade of tumors were determined from tissue samples by hematoxylin and eosin staining, while the presence of POU5F1/Oct-4 protein was determined by immunohistochemistry. POU5F1/Oct-4 expression levels in tissues obtained from patients with sentinel lymph node (SLN) and non-SLN metastasis and in tissues obtained from patients without lymph node metastases were compared. Results POU5F1/Oct-4 expression levels in breast cancer tissues were significantly higher in both the SLN metastasis and non-SLN metastasis groups (P = 0.003 and P = 0.030, respectively). Furthermore, POU5F1/Oct-4 expression was found to be associated to both histological (P = 0.01) and molecular type (P = 0.03). Thus, our data once again confirms the validity of the MSKCC nomogram. The area under curve (AUC) was 0.919 (95 % CI: 0.869–0.969, P

Triple-negative breast cancer is a high-risk breast cancer with poor survival rate. To date, there is a lack of targeted therapy for this type of cancer. One unique phenomenon is that inflammatory breast cancer is frequently triple negative. However, it is still ambiguous how inflammation influences triple-negative breast cancer growth and responding to chemotherapy. Herein, we investigated the levels of inflammation-associated enzyme, iNOS, in 20 triple-negative breast cancer patients' tumors, and examined its correlation with patients' responses to platinum-based neoadjuvant chemotherapy. Our studies showed that triple-negative breast cancer patients with attenuated iNOS levels in tumor cells after treatment showed better responses to platinum-based neoadjuvant chemotherapy than other triple-negative breast cancer patients. Our further in vitro studies confirmed that induction of proper levels of NO increased the resistance to cisplatin in triple-negative MDA-MB-231 cells. Our data suggest that aberrant high level of iNOS/NO are associated with less effectiveness of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer. Therefore, we propose to monitor iNOS levels as a new predictor for triple-negative breast cancer patient's response to platinum-based neoadjuvant chemotherapy. Moreover, iNOS/NO is considered as a potential target for combination therapy with platinum drugs for triple-negative breast cancer.

Objective: To study the relationship between expression of p57 KIP2 and prognosis and other clinicopathological parameters in invasive breast cancers. Methods: We assessed the expression of p57 KIP2 in 89 cases of invasive breast cancer and 20 cases of normal breast tissue by immunohistochemical methods and analyzed the results with SPSS software (ver. 16.0). Result: The positive expression rates of p57 KIP2 protein in the invasive breast cancers and surrounding normal tissue were 30.3% (27/89) and 65% (13/20), respectively. Cases with no p57 KIP2 expression exhibited a significantly higher post-operative distant metastasis rate than those with p57 KIP2 expression (37.9% vs. 14.8%; P = 0.01). DFS analysis showed that p57 KIP2 -/C-erbB-2+ tumors also exhibited a significantly higher post-operative distant metastasis rate than the other groups (66.7% vs. 29.2%; P = 0.007), as did p57 KIP2 -/p53+ tumors (64.3% vs. 22.7%; P = 0.001). Survival analysis revealed that p57 KIP2 was associated with breast cancer-specific survival overall (P = 0.045, log-rank test). Subgroup analysis demonstrated that individuals with p57 KIP2 -/C-erbB-2+tumors experienced significantly worse post-operative survival than those with p57 KIP2 - /C-erbB-2- or other tumors (P = 0.006, log-rank test). p57 KIP2 -/p53+ tumors were associated with significantly worse post-operative survival than p57 KIP2 -/p53- or other tumors (P = 0.001, log-rank test). Cox regression analysis showed that p57 KIP2 was a non-independent prognostic factor for breast cancer (P = 0.303). Conclusions: p57 KIP2 is expressed at low levels in invasive breast cancer and is associated with better overall survival rate and disease-free survival in breast cancer patients, but it was a non-independent prognostic factor for breast cancer. Thus, the connection between p57 KIP2 /p53 and p57 KIP2 /C-erbB-2 may provide biomarkers for