Oncotarget

Research Papers:

Distinct mechanisms by which two forms of miR-140 suppress the malignant properties of lung cancer cells

Valentina Flamini, Ed Dudley, Wen G. Jiang, Yuxin Cui _

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Oncotarget. 2018; 9:36474-36491. https://doi.org/10.18632/oncotarget.26356

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Abstract

Valentina Flamini1, Ed Dudley2, Wen G. Jiang1 and Yuxin Cui1

1Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

2Swansea University Medical School, Swansea University, Singleton Park, Swansea, SA2 8PP, UK

Correspondence to:

Yuxin Cui, email: cuiy7@cf.ac.uk

Keywords: microRNA; lung cancer; metabolism; RNA-Seq; signalling pathway

Received: June 26, 2018    Accepted: November 01, 2018    Published: November 23, 2018

ABSTRACT

In this study we attempted to determine the molecular mechanisms underlying the two mature products of pre-miR-140 (3p and 5p) in malignant properties of lung cancer cells. The differential expression of the two forms of miR-140 in both NSCLC tissues and cell lines was determined by quantitative real-time PCR (qRT-PCR). The effects of the miR-140 mimics on the malignant properties of lung cancer cells were evaluated using invasion assay, adhesion assay, tubule formation assay and metabolite profiling. Biotin-miRNA pulldown and transcriptome profiling by RNA-seq were utilized to distinguish their mRNA targets of the miR-140 strands. Their downstream signalling pathways were unveiled using a high-throughput antibody array. Although both strands of the miR-140 are downregulated in the NSCLC, miR-140-3p is more predominant compared to miR-140-5p in lung cancer cell lines. Both miR-140 mimics suppress the invasion of lung cancer cells and the inhibitory effect of the miR-140 on adhesion is cell-dependent. Tumor conditioned media from A549 cells after treatment with miR-140-3p mimic reduce the tubule formation ability of the endothelial cells. Metabolite profiling indicates the alteration of glycine in both lung cancer cells following treatment with miR-140 mimics. The data from the RNA-sequencing and antibody array indicate that two miR-140 strands present different targeting and signalling profiles despite the existence of mutual targets such as IGF1R and FOS. In conclusion, two forms of miR-140 both suppress the malignant properties of lung cancer cells but through distinct and multiple mechanisms.


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