Suppression of SIN3A by miR-183 Promotes Breast Cancer Metastasis.

Recent work has established that SWI-independent-3 (SIN3) chromatin modification complexes play key roles in cancer progression. We previously demonstrated that knockdown of SIN3A expression promotes human breast cancer cell invasion and metastasis; however, the levels of SIN3A in patient breast carcinoma are not known. We therefore examined SIN3A mRNA and protein in patient tissues and determined that SIN3A expression is lower in breast carcinoma relative to normal breast. Given the 3'-untranslated region (UTR) of SIN3A has several conserved binding sites for oncogenic miRNA, we hypothesized that SIN3A is targeted by miRNA and found that ectopic miR-183 results in decreased SIN3A in breast carcinoma cell lines. Functionally, we demonstrate that miR-183 promotes breast cancer cell migration and invasion in a SIN3A-dependent manner and ectopic miR-183 promotes metastasis in vivo. Patients with breast cancer with high levels of miR-183 and low levels of SIN3A have the shortest overall survival. Given the critical link between metastasis and survival in patients with breast cancer, it is of utmost importance to identify clinically relevant genes involved in metastasis. Here, we report for the first time the aberrant expression of the putative metastasis suppressing gene SIN3A in human breast cancers and propose a mechanism of SIN3A suppression by miR-183. IMPLICATIONS: SIN3A expression is decreased in metastatic breast cancer in part due to miR-183.

Virus-mediated EpoR76E Therapy Slows Optic Nerve Axonopathy in Experimental Glaucoma.

Glaucoma, a common cause of blindness, is currently treated by intraocular pressure (IOP)-lowering interventions. However, this approach is insufficient to completely prevent vision loss. Here, we evaluate an IOP-independent gene therapy strategy using a modified erythropoietin, EPO-R76E, which has reduced erythropoietic function. We used two models of glaucoma, the murine microbead occlusion model and the DBA/2J mouse. Systemic recombinant adeno-associated virus-mediated gene delivery of EpoR76E (rAAV.EpoR76E) was performed concurrent with elevation of IOP. Axon structure and active anterograde transport were preserved in both models. Vision, as determined by the flash visual evoked potential, was preserved in the DBA/2J. These results show that systemic EpoR76E gene therapy protects retinal ganglion cells from glaucomatous degeneration in two different models. This suggests that EPO targets a component of the neurodegenerative pathway that is common to both models. The efficacy of rAAV.EpoR76E delivered at onset of IOP elevation supports clinical relevance of this treatment.

Early experiences of employing consumer-providers in the VA.

OBJECTIVES: Following guidelines in the mental health strategic plan of the Department of Veterans Affairs (VA), VA began in 2005 to fund a number of new positions for consumer-providers (CPs)--that is, individuals with personal experience of serious mental illness who provide support services to others with serious mental illness, typically as clinical team members. This study explored the challenges of CP implementation in its early stages within the VA. METHODS: Four focus groups were conducted with a total of 59 VA CPs and 34 VA supervisors from across the United States. Group notes were coded by using a modified grounded theory approach to generate themes. RESULTS: Data from the groups suggest that hiring and employing CPs within VA has been feasible, beneficial, and acceptable to a majority of teammates. CPs reported experiencing some role confusion and resistance and fears among professional staff about how CPs would fit in. The authors make three recommendations on the basis of the focus group findings. First, CPs, traditional staff, and administrators need to be adequately prepared so that CPs can be effectively incorporated into clinical teams. Second, training for CPs varies widely, and efforts should be made to determine the best training package. Third, systems that are considering using CPs should establish a continuous quality improvement system to help evaluate CPs' performance and patient outcomes and to gather data to improve the knowledge base about CPs and their functions. CONCLUSIONS: CPs provide a wide range of recovery-oriented services and are valued by staff and consumers.