小RNA
体内
化学
细胞周期蛋白D1
细胞凋亡
体外
下调和上调
癌症研究
沙棘
细胞周期蛋白
细胞周期检查点
细胞周期蛋白B1
细胞周期
生物化学
生物
基因
细胞周期蛋白依赖激酶1
生物技术
食品科学
作者
Haili Wu,Chenglu Li,Mimi Cui,Huiqin Guo,Sen Chen,Jin'e Du,Hanqing Li,Zhuoyu Li
标识
DOI:10.1016/j.jff.2021.104780
摘要
• HPs60 treatment result in alteration of miRNA expression profile, among which, 29 up-regulated and 9 down-regulated. • Hsa-miR-195-5p, hsa-miR-497-5p and hsa-miR-1247-3p are the reliable targets of HPs60. • HPs60 up-regulate miR-195-5p/497-5p expression, suppresses that of cyclin D1/2/2 and cyclin E1, then leads to G1 arrest. • HPs60 promotes miR-1247-3p-mediated expression of caspase 2, and inhibits that of miR-195-5p/497-5p-mediated Bcl-2, ultimately induces apoptosis. 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.
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