Ginsenoside Rg3 Prevents Oncogenic Long Noncoding RNA ATXN8OS from Inhibiting Tumor-Suppressive microRNA-424-5p in Breast Cancer Cells
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 fou...
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doaj-78ad65c3044f4e82b33d441d3f8d14882021-01-19T00:04:48ZengMDPI AGBiomolecules2218-273X2021-01-011111811810.3390/biom11010118Ginsenoside Rg3 Prevents Oncogenic Long Noncoding RNA ATXN8OS from Inhibiting Tumor-Suppressive microRNA-424-5p in Breast Cancer CellsHeejoo Kim0Hwee Won Ji1Hyeon Woo Kim2Sung Hwan Yun3Jae Eun Park4Sun Jung Kim5Department of Life Science, Dongguk University-Seoul, Goyang 10326, KoreaDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, KoreaDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, KoreaDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, KoreaDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, KoreaDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, KoreaGinsenoside 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.https://www.mdpi.com/2218-273X/11/1/118ceRNACpG methylationginsenoside Rg3long noncoding RNAmicroRNA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Heejoo Kim Hwee Won Ji Hyeon Woo Kim Sung Hwan Yun Jae Eun Park Sun Jung Kim |
spellingShingle |
Heejoo Kim Hwee Won Ji Hyeon Woo Kim Sung Hwan Yun Jae Eun Park Sun Jung Kim Ginsenoside Rg3 Prevents Oncogenic Long Noncoding RNA ATXN8OS from Inhibiting Tumor-Suppressive microRNA-424-5p in Breast Cancer Cells Biomolecules ceRNA CpG methylation ginsenoside Rg3 long noncoding RNA microRNA |
author_facet |
Heejoo Kim Hwee Won Ji Hyeon Woo Kim Sung Hwan Yun Jae Eun Park Sun Jung Kim |
author_sort |
Heejoo Kim |
title |
Ginsenoside Rg3 Prevents Oncogenic Long Noncoding RNA ATXN8OS from Inhibiting Tumor-Suppressive microRNA-424-5p in Breast Cancer Cells |
title_short |
Ginsenoside Rg3 Prevents Oncogenic Long Noncoding RNA ATXN8OS from Inhibiting Tumor-Suppressive microRNA-424-5p in Breast Cancer Cells |
title_full |
Ginsenoside Rg3 Prevents Oncogenic Long Noncoding RNA ATXN8OS from Inhibiting Tumor-Suppressive microRNA-424-5p in Breast Cancer Cells |
title_fullStr |
Ginsenoside Rg3 Prevents Oncogenic Long Noncoding RNA ATXN8OS from Inhibiting Tumor-Suppressive microRNA-424-5p in Breast Cancer Cells |
title_full_unstemmed |
Ginsenoside Rg3 Prevents Oncogenic Long Noncoding RNA ATXN8OS from Inhibiting Tumor-Suppressive microRNA-424-5p in Breast Cancer Cells |
title_sort |
ginsenoside rg3 prevents oncogenic long noncoding rna atxn8os from inhibiting tumor-suppressive microrna-424-5p in breast cancer cells |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2021-01-01 |
description |
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. |
topic |
ceRNA CpG methylation ginsenoside Rg3 long noncoding RNA microRNA |
url |
https://www.mdpi.com/2218-273X/11/1/118 |
work_keys_str_mv |
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