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Exp Mol Med. 2018 Sep 12;50(9):121. doi: 10.1038/s12276-018-0146-6.

Inactivation of Stat3 and crosstalk of miRNA155-5p and FOXO3a contribute to the induction of IGFBP1 expression by beta-elemene in human lung cancer.

Author information

1
Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical Collage, Guangzhou University of Chinese Medicine, 510120, Guangzhou, Guangdong Province, China.
2
Department of Medical Oncology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical Collage, Guangzhou University of Chinese Medicine, 510120, Guangzhou, Guangdong Province, China.
3
Laboratory Animal Research Center, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical Collage, Guangzhou University of Chinese Medicine, 510120, Guangzhou, Guangdong Province, China.
4
Department of Medical Oncology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical Collage, Guangzhou University of Chinese Medicine, 510120, Guangzhou, Guangdong Province, China. haibozh@aliyun.com.
5
Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical Collage, Guangzhou University of Chinese Medicine, 510120, Guangzhou, Guangdong Province, China. haibozh@aliyun.com.
6
Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical Collage, Guangzhou University of Chinese Medicine, 510120, Guangzhou, Guangdong Province, China. hann2012@outlook.com.
7
Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical Collage, Guangzhou University of Chinese Medicine, 510120, Guangzhou, Guangdong Province, China. hann2012@outlook.com.

Abstract

β-Elemene, an active component of natural plants, has been shown to exhibit anticancer properties. However, the detailed mechanism underlying these effects has yet to be determined. In this study, we show that β-elemene inhibits the growth of lung cancer cells. Mechanistically, we found that β-elemene decreased the phosphorylation of signal transducer and activator of transcription 3 (Stat3) and miRNA155-5p mRNA but induced the protein expression of human forkhead box class O (FOXO)3a; the latter two were abrogated in cells with overexpressed Stat3. Notably, miRNA155-5p mimics reduced FOXO3a luciferase reporter activity in the 3-UTR region and protein expression, whereas overexpressed FOXO3a countered the reduction of the miRNA155-5p levels by β-elemene. Moreover, β-elemene increased the mRNA and protein expression levels as well as promoter activity of insulin-like growth factor-binding protein 1 (IGFBP1); this finding was not observed in cells with a silenced FOXO3a gene and miRNA155-5p mimics. Finally, silencing of IGFBP1 blocked β-elemene-inhibited cell growth. Similar findings were observed in vivo. In summary, our results indicate that β-elemene increases IGFBP1 gene expression via inactivation of Stat3 followed by a reciprocal interaction between miRNA155-5p and FOXO3a. This effect leads to inhibition of human lung cancer cell growth. These findings reveal a novel molecular mechanism underlying the inhibitory effects of β-elemene on lung cancer cells.

PMID:
30209296
PMCID:
PMC6135838
DOI:
10.1038/s12276-018-0146-6
[Indexed for MEDLINE]
Free PMC Article

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