• Dawoon Jeong, Juyeon Ham, Sungbin Park, Hyeon Woo Kim, Heejoo Kim, Hwee Won Ji, and Sun Jung Kim.
• Department of Life Science, Dongguk University-Seoul, Goyang, Republic of Korea.
• Am. J. Chin. Med. 2019 Jan 1; 47 (7): 1643-1658.

AbstractGinsenoside Rh2, a major bioactive ingredient abundant in red ginseng, has an antiproliferative effect on various cancer cells. In this study, we report a novel long noncoding RNA, C3orf67-AS1, which was identified as being hypermethylated at a CpG site of the promoter by Rh2 in MCF-7 cancer cells. Rh2-induced hypermethylation was responsible for the lower gene expression; the expression was recovered following treatment with a methyltransferase inhibitor, 5-aza-2'-deoxycytidine. When C3orf67-AS1 was downregulated by a siRNA, the cell growth rate was decreased, demonstrating the RNA's oncogenic activity. Accordingly, breast cancer patients showed a lower methylation and higher expression level of C3orf67-AS1. Within 800 kb flanking C3orf67-AS1 on the chromosome, eight genes were found, and four genes including C3orf67 (the sense strand gene of C3orf67-AS1) were downregulated by Rh2. In particular, C3orf67 was downregulated when C3orf67-AS1 was suppressed by a siRNA; however, the expression of C3orf67-AS1 was not affected by C3orf67. Taken together, this study identifies a novel noncoding RNA, C3orf67-AS1, of which the expression could be suppressed by Rh2 via promoter methylation, thereby mediating the anti-proliferative effect of the ginsenoside.

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