title: Suppression of tumor cell invasiveness and in vivo tumor growth by microRNA-874 in non-small cell lung cancer.
abstract: 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.
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, United States.
authors.forename: Divya
authors.initials: D
authors.lastname: Kesanakurti
authors.forename: Dilip Rajasekhar
authors.initials: DR
authors.lastname: Maddirela
authors.forename: Subramanyam
authors.initials: S
authors.lastname: Chittivelu
authors.forename: Jasti S
authors.initials: JS
authors.lastname: Rao
authors.forename: Chandramu
authors.initials: C
authors.lastname: Chetty
mesh_terms: D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D002455:Cell Division / Q000235:genetics*; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C561946:MIRN874 microRNA, human; D035683:MicroRNAs