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Suppression of Tumor Cell Invasiveness and In Vivo Tumor Growth by MicroRNA-874 in Non-Small Cell Lung Cancer

journal contribution
posted on 03.01.2014, 00:00 by Divya Kesanakurti, Dilip Rajasekhar Maddirela, Subramanyam Chittivelu, Jasti S. Rao, Chandramu Chetty
MicroRNAs are a novel family of small non-coding RNAs that regulate the expression of several genes involved in normal development as well as human disorders including cancer. Here we show that miR-874 plays a tumor suppressor role in non-small cell lung cancer (NSCLC) in vitro and in vivo. In silico target prediction analysis revealed numerous genes associated with tumor progression including MMP-2 and uPA as the putative target genes of miR-874. Our preliminary in situ hybridization experiments demonstrated the diminution of miR-874 expression in lung cancer tissues compared to their normal counter parts. Overexpression of miR-874 in CD133-positive cancer stem cell (CSC) population led to a significant loss in CSC-phenotype and enhanced sphere de-differentiation into epithelial-like cells. Restoration of miR-874 expression drastically reduced cell invading ability in comparison to mock and control-miR-treated cells by suppressing the protein levels of MMP-2 and uPA. In in vivo experiments, miR-874 treatment decreased orthotopic tumor growth in nude mice compared to mock and control-miR treatments. Further, the immunoreactivity of human anti-MMP-2 and anti-uPA was significantly reduced in tumor sections from mice that received miR-874 treatment. In conclusion, our study highlights the possible tumor suppressor role of miR-874 in NSCLC-initiating cells and suggests miR-874 as a potential target in the treatment of NSCLC.

Funding

This research was supported by Caterpillar Inc., and OSF Saint Francis Medical Center, Peoria, IL, USA (to JSR).

History

Publisher Statement

NOTICE: This is the author’s version of a work that was accepted for publication in Biochemical and Biophysical Research Communications. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochemical and Biophysical Research Communications, Vol 434, Issue 3, 2013 DOI:10.1016/j.bbrc.2013.03.132

Publisher

Elsevier Inc.

Language

en_US

issn

1090-2104

Issue date

01/05/2013

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