Polyphenols from Hippophae rhamnoides suppressed colon cancer growth by regulating miRNA-mediated cell cycle arrest and apoptosis in vitro and in vivo
Haili Wu, Chenglu Li, Mimi Cui, Huiqin Guo, Sen Chen, Jin’e Du, Hanqing Li, Zhuoyu Li
Abstract
Colorectal cancer (CRC) is the most common gastrointestinal cancer. Hippophae rhamnoides are reported to possess a variety of active substances. MiRNAs are new therapeutic targets. Here, it found that Hippophae rhamnoides L. polyphenols (named as HPs60) exhibited significant anti-colon cancer activity in vitro and in vivo. And the main components were identified by LC-MS as kaempferol and its derivatives. Subsequently, by RNA-sequencing and searching GEO and TCGA database, three reliable miRNAs including hsa-miR-195-5p, hsa-miR-497-5p and hsa-miR-1247-3p were eventually screened. As expected, hsa-miR-195-5p and hsa-miR-497-5p were upregulated upon HPs60 treatment, while hsa-miR-1247-3p was downregulated. Furthermore, HPs60 remarkably suppressed the expression of cyclinD1, cyclinD2, cyclinD3, cyclinE1 and Bcl-2, which are the targets of miR-195-5p and miR-497-5p. Correspondingly, HPs60 promoted expression of caspase-2, a target gene of miR-1247-3p. All of these results suggest that HPs60 may explore as natural bioactive ingredients and reveal the potential therapeutic targets responsible for HPs60 against CRC.