LncRNA GACAT3 acts as a competing endogenous RNA of HMGA1 and alleviates cucurbitacin B-induced apoptosis of gastric cancer cells.

Long non-coding RNAs (lncRNAs) have been demonstrated to perform important roles in cancer development. Previously, we have shown that lncRNA gastric cancer-associated transcript 3 (GACAT3) is overexpressed in gastric cancer and acts as a downstream target of interleukin 6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling. However, the role of GACAT3 in regulating gastric cancer cell growth remains unclear. In this study, we demonstrate that GACAT3 acts as a competing endogenous RNA of high mobility group A1 (HMGA1), a typical oncogene that is overexpressed in most types of cancer, based on a search for common miRNA-binding sites and on experiments involving in vitro cell transfection with synthesized miRNA mimics. Furthermore, knockdown of GACAT3 by its specific siRNA resulted in significantly decreased cell proliferation in gastric cancer cells, similar to the effect of an HMGA1 knockdown. Moreover, GACAT3 overexpression alleviated the apoptosis induced by cucurbitacin B, which is a widely used anticancer drug. Mechanistically, GACAT3 amplified STAT3 expression and decreased the level of the apoptosis gene bcl-2-associated X protein (BAX). Thus, our study provides fundamental information regarding GACAT3, which could be a valuable target for gastric cancer therapy.