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

Flamini, Valentina ORCID: https://orcid.org/0000-0003-1337-7125, Dudley, Ed, Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111 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:	05 May 2023 10:34
URI:	https://orca.cardiff.ac.uk/id/eprint/117144

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