Exploration of inhibitory mechanisms of curcumin in lung cancer metastasis using a miRNA- transcription factor-target gene network.

Qung-yong Chen,De-Min Jiao,Jian Wang,Li Yan,Xia-Li Tang,Li-Shan Wang,Hui-Zhen Hu,You Li,Jun Chen

doi:10.1371/journal.pone.0172470

Qung-yong Chen, De-Min Jiao + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0172470

Copy DOI

Abstract

The present study was aimed to unravel the inhibitory mechanisms of curcumin for lung cancer metastasis via constructing a miRNA-transcription factor (TF)-target gene network. Differentially expressed miRNAs between human high-metastatic non-small cell lung cancer 95D cells treated with and without curcumin were identified using a TaqMan human miRNA array followed by real-time PCR, out of which, the top 6 miRNAs (miR-302b-3p, miR-335-5p, miR-338-3p, miR-34c-5p, miR-29c-3p and miR-34a-35p) with more verified target genes and TFs than other miRNAs as confirmed by a literature review were selected for further analysis. The miRecords database was utilized to predict the target genes of these 6 miRNAs, TFs of which were identified based on the TRANSFAC database. The findings of the above procedure were used to construct a miRNA-TF-target gene network, among which miR-34a-5p, miR-34c-5p and miR-302b-3p seemed to regulate CCND1, WNT1 and MYC to be involved in Wnt signaling pathway through the LEF1 transcription factor. Therefore, we suggest miR-34a-5p/miR-34c-5p/miR-302b-3p —LEF1—CCND1/WNT1/MYC axis may be a crucial mechanism in inhibition of lung cancer metastasis by curcumin.

Highlights

Lung cancer, predominantly non-small-cell lung cancer (NSCLC), is the most common cause of cancer mortality in the United States, with an estimated 158,080 cancer deaths occurred in 2016 [1]
It was decreased to 49% in cells exposed to 20 μM curcumin compared with the control group (p < 0.01)
By comprehensively analyzing the experimentally validated and all potential target genes of these 6 miRNAs, our study suggested miR-34a-5p, miR-34c-5p and miR-302b-3p seemed to be important in inhibition of lung cancer metastasis by curcumin because their target genes (e.g. CCND1, Wnt family member 1 (WNT1), myelocytomatosis viral oncogene homolog (MYC) and lymphoid enhancer binding factor 1 (LEF1)) were significantly enriched in metastasis related pathways (Wnt signaling pathway and Focal adhesion)

Summary

Introduction

Predominantly non-small-cell lung cancer (NSCLC), is the most common cause of cancer mortality in the United States, with an estimated 158,080 cancer deaths occurred in 2016 [1]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Objectives

Methods

Results

Discussion

Conclusion