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In the western world the incidence of adenocarcinomas of the esophagus and the gastroesophageal junction (GEJ) is increasing. A better understanding of molecular aberrations associated with gastric cancer is needed in order to identify new diagnostic and therapeutic strategies. We examined the expression, regulation and prognostic value of HOX transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA) from the HOX cluster. Biopsies were collected from fourty patients undergoing surgery for adenocarcinoma of the stomach, esophagus or GEJ. Clinico-pathological variables with possible prognostic value were analyzed to identify independent prognostic factors. HOTAIR expression was measured by qRT-PCR in human gastric adenocarcinoma cells and cell proliferation and migration was followed real-time using the xCELLigence impedance analysis. High HOTAIR expression in resected gastric, esophageal and GEJ adenocarcinomas was an independent predictor of poor prognosis. We found that over-expression of HOTAIR doubled proliferation in HFE145 gastric cells. miR-449 and inhibition of HDACs (miR-449 targets) by Vorinostat or siRNA reduced the expression of HOTAIR in vitro. HOTAIR expression was not controlled via miR-449 regulation of p53. We propose a role for HDAC as a regulator of HOTAIR expression.

journal of  gastric disorders and therapy

miR-449 and HDAC modulates HOTAIR Expression which Predicts Poor Prognosis in Resected Gastroesophageal Adenocarcinomas and Doubles Proliferation Rate in HFE145 Cells