Department of Life Science, Dongguk University-Seoul, Goyang 10326, Korea.
Biomolecules. 2021 Jan 18;11(1):118. doi: 10.3390/biom11010118.
Ginsenoside Rg3 exerts antiproliferation activity on cancer cells by regulating diverse noncoding RNAs. However, little is known about the role of long noncoding RNAs (lncRNAs) or their relationship with competitive endogenous RNA (ceRNA) in Rg3-treated cancer cells. Here, a lncRNA (ATXN8OS) was found to be downregulated via Rg3-mediated promoter hypermethylation in MCF-7 breast cancer cells. SiRNA-induced downregulation of ATXN8OS decreased cell proliferation but increased apoptosis, suggesting that the noncoding RNA possessed proproliferation activity. An in silico search for potential ATXN8OS-targeting microRNAs (miRs) identified a promising candidate (miR-424-5p) based on its high binding score. As expected, miR-424-5p suppressed proliferation and stimulated apoptosis of the MCF-7 cells. The in silico miR-target-gene prediction identified 200 potential target genes of miR-424-5p, which were subsequently narrowed down to seven that underwent hypermethylation at their promoter by Rg3. Among them, three genes (EYA1, DACH1, and CHRM3) were previously known oncogenes and were proven to be oppositely regulated by ATXN8OS and miR-424-5p. When taken together, Rg3 downregulated ATXN8OS that inhibited the tumor-suppressive miR-424-5p, leading to the downregulation of the oncogenic target genes.
人参皂苷 Rg3 通过调节多种非编码 RNA 对癌细胞发挥抗增殖活性。然而，关于长非编码 RNA (lncRNA)或它们与竞争内源性 RNA (ceRNA)在 Rg3 处理的癌细胞中的关系知之甚少。在这里，发现在 MCF-7 乳腺癌细胞中，通过 Rg3 介导的启动子超甲基化导致 lncRNA (ATXN8OS)下调。ATXN8OS 的 siRNA 诱导下调降低了细胞增殖，但增加了细胞凋亡，表明该非编码 RNA 具有促增殖活性。对潜在的 ATXN8OS 靶向 microRNAs (miRs) 的计算搜索根据其高结合评分确定了一个有前途的候选物(miR-424-5p)。正如预期的那样，miR-424-5p 抑制 MCF-7 细胞的增殖并刺激细胞凋亡。miR 靶基因预测的计算表明，miR-424-5p 的 200 个潜在靶基因随后被 Rg3 下调其启动子的甲基化。其中，三个基因（EYA1、DACH1 和 CHRM3）是先前已知的癌基因，被证明受 ATXN8OS 和 miR-424-5p 的反向调节。总的来说，Rg3 下调了抑制肿瘤抑制性 miR-424-5p 的 ATXN8OS，导致致癌靶基因下调。
