The Curcumin Analog Da0324 Inhibits the Proliferation of Gastric Cancer Cells Via HOTAIRM1/miR-29b-1-5p/PHLPP1 Axis

Abstract

Background Our previous study has shown that Da0324, a curcumin analog, has significantly improved stability and antitumor activity. However, the molecular mechanisms of action of Da0324 remains poorly understood. Long non-coding RNA (lncRNA) has been certifed to play a key role in tumor progression. Here, we aim to investigate the molecular mechanisms underlying the anti-cancer activities of Da0324 through regulation of lncRNA HOTAIRM1. Methods Gastric cancer cell lines were treated with Da0324 and/or transfected with lentiviral vector expressing HOTAIRM1 shRNA, and/or miR-29b-1-5p mimics and/or small interference RNA (siRNA) against PHLPP1, or HOTAIRM1 siRNA or lentiviral vector expressing HOTAIRM1, as required. The expression of HOTAIRM1, miR-29b-1-5p and PHLPP1 in GC cells were determined by Real-Time PCR. Cell growth was examined by CCK-8 assay and colony formation assay in vitro. The targeted relationship between HOTAIRM1 and miR-29b-1-5p was verifed by luciferase reporter gene assay. Western blot was utilized to investigate PHLPP1 protein expression levels. Results Da0324 increased the expression of HOTAIRM1 in GC cells. HOTAIRM1 expression was significantly down-regulated in GC tissues, and the low expression of HOTAIRM1 was associated with the shorter survival rate of GC patients based on TCGA database. Knockdown of HOTAIRM1 promoted GC cell proliferation whereas overexpression of HOTAIRM1 inhibited GC cell proliferation as detected by CCK-8 and colony formation assays. Moreover, knockdown of HOTAIRM1 reversed the Da0324-mediated growth inhibition of GC cells. Furthermore, HOTAIRM1 acted as a sponge for miR-29b-1-5p and PHLPP1 is regulated by the HOTAIRM1/miR-29b-1-5p axis in GC cells. Overexpression of miR-29b-1-5p or knockdown of PHLPP1 reversed the ability of Da0324 to inhibit the growth of GC cells. Conclusions Our data suggest that Da0324 exerts antitumor activity by regulating HOTAIRM1/miR-29b-1-5p/PHLPP1 axis in GC cell, and provide new insights into the anti-cancer mechanism of Da0324.