Format

Send to

Choose Destination
J Exp Clin Cancer Res. 2019 Nov 29;38(1):479. doi: 10.1186/s13046-019-1478-3.

Inhibition of lung cancer growth and metastasis by DHA and its metabolite, RvD1, through miR-138-5p/FOXC1 pathway.

Author information

1
Department of Pathology, Nanjing Medical University, Nanjing, 210029, People's Republic of China.
2
Department of Bioinformatics, Nanjing Medical University, Nanjing, 210029, People's Republic of China.
3
School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, People's Republic of China.
4
Department of Pathology, The Second People's Hospital of Nantong, Nantong, 226000, People's Republic of China.
5
School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, People's Republic of China. azzhao@gdut.edu.cn.
6
Department of Biotherapy, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, People's Republic of China. panjinshun@njmu.edu.cn.

Abstract

BACKGROUND:

Non small cell lung cancer (NSCLC) is one of the most common cancers in the world. DHA is known to be capable of suppressing NSCLC cell proliferation and metastasis. However, the mechanisms by which DHA exhibits its antitumor effects are unknown. Here we aimed to identify the effects and mechanisms of DHA and its metabolites on lung cancer cell growth and invasion.

METHODS:

As measures of cell proliferation and invasion ability, the cell viability and transwell assays were used in vitro. Transgenic mfat-1 mice, which convert ω-6 PUFAs to ω-3 PUFAs, were used to detect the effect of endogenous DHA on tumor transplantation. An LC - MS/MS analysis identified the elevation of several eicosanoid metabolites of DHA. By using qPCR miRNA microarray, online prediction software, luciferase reporter assays and Western blot analysis, we further elucidated the mechanisms.

RESULTS:

Addition of exogenous DHA inhibited the growth and invasion in NSCLC cells in vitro. Endogenously produced DHA attenuated LLC-derived tumor growth and metastasis in the transgenic mfat-1 mice. Among the elevation of DHA metabolites, resolvin D1 (RvD1) significantly contributed to the inhibition in cell growth and invasion. MiRNA microarray revealed that the level of miR-138-5p was significantly increased after RvD1 treatment. MiR-138-5p mimics decreased cell viability and invasion; while miR-138-5p inhibitor abolished RvD1-mediated suppression of cell viability and invasion. The expression of FOXC1 was significantly reduced upon overexpression of miR-138-5p while luciferase reporter assay showed that FOXC1 was a direct target of miR-138-5p. In vivo, endogenous DHA by the mfat-1 transgene enhanced miR-138-5p expression and decreased FOXC1 expression. Furthermore, overexpression of FOXC1 reversed the inhibition in cell viability and invasion induced by RvD1 treatment.

CONCLUSIONS:

These data identified the RvD1/miR-138-5p/FOXC1 pathway as a novel mechanism by DHA and its metabolite, RvD1, and the potential of targeting such pathway as a therapeutic strategy in treating NSCLC.

KEYWORDS:

FOXC1; Growth and invasion; Lung cancer; Resolvin D1; miR-138-5p

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center