Downregulation of LINC01021 by curcumin analog Da0324 inhibits gastric cancer progression through activation of P53.

ABSTRACT

Curcumin is a safe, cost-effective natural agent with multiple targets that displays therapeutic potential in cancer. Recently, we reported a novel curcumin analog, Da0324, which exhibited significantly improved stability and anti-cancer activity. However, the molecular mechanism underlying the anti-cancer activity of Da0324 remains largely unknown. Long non-coding RNAs have been shown to play important roles in cancer development and progression and may be potential targets for cancer therapy. Here, we showed that Da0324 treatment down-regulated the expression of LINC01021 in gastric cancer cells. Da0324 treatment or knockdown of LINC01021 by antisense oligos significantly inhibited gastric cancer cell growth, and also up-regulated P53 expression and down-regulated Bcl-2 expression in vitro and in vivo. Furthermore, Da0324 treatment or knockdown of LINC01021 in gastric cancer cells suppressed cell migration, invasion and epithelial-mesenchymal transition (EMT), as well as induced apoptosis and autophagy. In addition, overexpression of LINC01021 promoted growth and EMT, inhibited P53 expression and increased Bcl-2 expression in gastric cancer cells. Finally, overexpression of LINC01021 reversed the anti-cancer effect of Da0324. Our findings indicate a novel anti-cancer mechanism for Da0324, and that LINC01021 might be a potential therapeutic target for the treatment of gastric cancer.