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BackgroundTumor metastasis is responsible for 90% of cancer-related deaths. Recently, a strong link between microRNA dysregulation and human cancers has been established. However, the molecular mechanisms through which microRNAs regulate metastasis and cancer progression remain unclear.MethodsWe analyzed the reciprocal expression regulation of miR-31 and SOX4 in esophageal squamous and adenocarcinoma cell lines by qRT-PCR and Western blotting using overexpression and shRNA knock-down approaches. Furthermore, methylation studies were used to assess epigenetic regulation of expression. Functionally, we determined the cellular consequences using migration and invasion assays, as well as proliferation assays. Immunoprecipitation and ChIP were used to identify complex formation of SOX4 and co-repressor components.ResultsHere, we report that SOX4 promotes esophageal tumor cell proliferation and invasion by silencing miR-31 via activation and stabilization of a co-repressor complex with EZH2 and HDAC3. We demonstrate that miR-31 is significantly decreased in invasive esophageal cancer cells, while upregulation of miR-31 inhibits growth, migration and invasion of esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) cell lines. miR-31, in turn, targets SOX4 for degradation by directly binding to its 3′-UTR. Additionally, miR-31 regulates EZH2 and HDAC3 indirectly. SOX4, EZH2 and HDAC3 levels inversely correlate with miR-31 expression in ESCC cell lines. Ectopic expression of miR-31 in ESCC and EAC cell lines leads to down regulation of SOX4, EZH2 and HDAC3. Conversely, pharmacologic and genetic inhibition of SOX4 and EZH2 restore miR-31 expression. We show that SOX4, EZH2 and HDAC3 form a co-repressor complex that binds to the miR-31 promoter, repressing miR-31 through an epigenetic mark by H3K27me3 and by histone acetylation. Clinically, when compared to normal adjacent tissues, esophageal tumor samples show upregulation of SOX4, EZH2, and HDAC3, and EZH2 expression is significantly increased in metastatic ESCC tissues.ConclusionsThus, we identified a novel molecular mechanism by which the SOX4, EZH2 and miR-31 circuit promotes tumor progression and potential therapeutic targets for invasive esophageal carcinomas.

African descent is a well-documented risk factor for glaucoma development, progression, and medical and surgical failure. We reviewed the literature for evidence of outcomes disparities between Black and White populations after trabeculectomy, Ex-PRESS shunt, viscocanalostomy, canaloplasy, tube shunt, laser trabeculoplasty, and cyclophotocoagulation. There are reports of decreased surgical success in Black patients after trabeculectomy, Ex-PRESS shunt, tube-shunt, and canaloplasty. At this time, there is no strong evidence that any procedure is more effective for intraocular pressure control than standard trabeculectomy for Black patients. Furthermore, there is insufficient evidence to recommend any particular secondary intervention over another, despite differences in inflammation and bleb-dependence. There is a need for randomized, controlled trials to assess race as a risk factor for failure after non-penetrating filtration surgery (NPFS). There is also a need for data on the efficacy of minimally invasive glaucoma surgery (MIGS) in Black populations.

Purpose To describe a case of acute macular neuroretinopathy (AMN) in a patient immediately following administration of the Pfizer-BioNTech COVID-19 vaccine. Observations The patient complained of paracentral scotoma supported by paracentral visual field loss on multiple Humphrey visual fields that corresponded to outer retinal pathology on optical coherence tomography. The patient's symptoms resolved without treatment. Conclusions and Importance We conclude that the clinical testing demonstrated findings consistent with AMN. AMN may be an exceedingly rare adverse ocular effect of a novel vaccine and likely only in the setting of multiple other risk factors. Despite this, we strongly recommend vaccination against COVID-19.

Benign peripheral nerve sheath tumors such as schwannoma and neurofibroma have long been considered distinct entities. Recently, hybrid tumors demonstrating combined morphological features of neurofibroma and schwannoma have been described, primarily in dermal locations. Only 1 case of hybrid peripheral nerve sheath tumor of the orbit has been reported in the literature. Hybrid morphology is important to recognize because of its association with the neurofibromatoses, including schwannomatosis; however, the paucity of literature on orbital hybrid peripheral nerve sheath tumor poses a diagnostic challenge. This article describes a case of hybrid neruofibroma/schwannoma of the orbit arising from the supraorbital nerve with clinicopathologic correlation.