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

Flamini, Valentina, Dudley, Ed, Jiang, Wen Guo and Cui, Yuxin 2018. Distinct mechanisms by which two forms of miR-140 suppress the malignant properties of lung cancer cells. Oncotarget 2018 (9) 10.18632/oncotarget.26356

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Impact Journals
ISSN: 1949-2553
Funders: Cancer Research Wales, Cardiff China Medical Scholarship
Date of First Compliant Deposit: 27 November 2018
Date of Acceptance: 1 November 2018
Last Modified: 28 Nov 2018 10:00
URI: http://orca.cf.ac.uk/id/eprint/117144

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