title: Downregulation of miR-486-5p contributes to tumor progression and metastasis by targeting protumorigenic ARHGAP5 in lung cancer.
abstract: We have previously shown that miR-486-5p is one of the most downregulated micro RNAs in lung cancer. The objective of the study was to investigate the role of miR-486-5p in the progression and metastasis of non-small-cell lung cancer (NSCLC). We evaluated miR-486-5p expression status on 76 frozen and 33 formalin-fixed paraffin-embedded tissues of NSCLC by quantitative reverse transcriptase PCR to determine its clinicopathologic significance. We then performed function analysis of miR-486-5p to determine its potential roles on cancer cell migration and invasion in vitro and metastasis in vivo. We also investigated the target genes of miR-486-5p in lung tumorigenesis. miR-486-5p expression level was significantly lower in lung tumors compared with their corresponding normal tissues (P<0.0001), and associated with stage (P=0.0001) and lymph node metastasis of NSCLC (P=0.0019). Forced expression of miR-486-5p inhibited NSCLC cell migration and invasion in vitro and metastasis in mice by inhibiting cell proliferation. Furthermore, ectopic expression of miR-486-5p in cancer cells reduced ARHGAP5 expression level, whereas miR-486-5p silencing increased its expression. Luciferase assay demonstrated that miR-486-5p could directly bind to the 3'-untranslated region of ARHGAP5. The expression level of miR-486-5p was inversely correlated with that of ARHGAP5 in lung tumor tissues (P=0.0156). Reduced expression of ARHGAP5 considerably inhibited lung cancer cell migration and invasion, resembling that of miR-486-5p overexpression. miR-486-5p may act as a tumor-suppressor contributing to the progression and metastasis of NSCLC by targeting ARHGAP5. miR-486-5p would provide potential diagnostic and therapeutic targets for the disease.
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, China.
authors.forename: X
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, China.
authors.forename: R
authors.initials: R
authors.lastname: Han
authors.affiliation: Department of Pathology, Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Tumor Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, China.
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, China.
authors.forename: L
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Pathology, Tumor Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, China.
authors.forename: X
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: K
authors.initials: K
authors.lastname: Mannoor
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Deepak
authors.affiliation: Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Donahue
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Stass
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, China.
authors.forename: L
authors.initials: L
authors.lastname: Xing
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: F
authors.initials: F
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics*; D020690:GTPase-Activating Proteins / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C513043:ARHGAP5 protein, human; D020690:GTPase-Activating Proteins; C560945:MIRN486 microRNA, human; D035683:MicroRNAs