miR-8 modulates cytoskeletal regulators to influence cell survival and epithelial organization in Drosophila wings.

The miR-200 microRNA family plays important tumor suppressive roles. The sole Drosophila miR-200 ortholog, miR-8 plays conserved roles in Wingless, Notch and Insulin signaling - pathways linked to tumorigenesis, yet homozygous null animals are viable and often appear morphologically normal. We observed that wing tissues mosaic for miR-8 levels by genetic loss or gain of function exhibited patterns of cell death consistent with a role for miR-8 in modulating cell survival in vivo. Here we show that miR-8 levels impact several actin cytoskeletal regulators that can affect cell survival and epithelial organization. We show that loss of miR-8 can confer resistance to apoptosis independent of an epithelial to mesenchymal transition while the persistence of cells expressing high levels of miR-8 in the wing epithelium leads to increased JNK signaling, aberrant expression of extracellular matrix remodeling proteins and disruption of proper wing epithelial organization. Altogether our results suggest that very low as well as very high levels of miR-8 can contribute to hallmarks associated with cancer, suggesting approaches to increase miR-200 microRNAs in cancer treatment should be moderate.

Severe Hypokalemia Causing Ventricular Tachycardia: A Case Report.

Hypokalemia and hyperosmolar hyperglycemic syndrome (HHS) are two reversible but potentially fatal disorders that are important to identify and treat urgently. A 43-year-old patient presented to the ED with altered mental status and slurred speech, difficulty communicating, left-sided facial droop, and stool incontinence according to emergency medical services. This was preceded by 1.5 weeks of nausea, vomiting, polydipsia, and weight loss. On presentation, the patient was found tachycardic and tachypneic, with uncertain neurological deficits on physical exam, hyperglycemia, and electrocardiogram (EKG) abnormalities. Lab data were consistent with hyperosmolar hyperglycemic nonketotic coma. This case provides two important clinical scenarios in which cardiac EKG abnormalities and focal neurological deficits are the product of hyperosmolality and electrolyte abnormalities. Hypokalemia with EKG abnormalities consistent with a potential ischemic disease can progress into wide complex tachycardia and ventricular fibrillation. Hyperosmolar hyperglycemia may manifest with focal neurological deficits and without the classical presentation of a coma. Careful consideration of EKG and lab values in the context of clinical presentation may provide clues to resolvable etiologies. We report a case of a patient who presented to the ED with hypokalemia and HHS, both reversible but potentially fatal disorders that are important to identify and urgently treat.