title: microRNA-590 suppresses the tumorigenesis and invasiveness of non-small cell lung cancer cells by targeting ADAM9.
abstract: microRNAs (miRNAs), a family of small non-coding RNA molecules, are implicated in cancer growth and progression. In the present study, we examined the expression and biological roles of miR-590 in non-small cell lung cancer (NSCLC). Compared to normal lung tissues, miR-590 expression was downregulated in primary NSCLCs and, to a greater extent, in corresponding brain metastases. NSCLC cell lines with high metastatic potential had significantly (P < 0.05) lower levels of miR-590 than those with low metastatic potential. Re-expression of miR-590 suppressed NSCLC cell proliferation, colony formation, migration, and invasion in vitro and tumorigenesis in vivo. In contrast, inhibition of miR-590 enhanced the migration and invasion of NSCLC cells. Mechanistic studies revealed that a disintegrin and metalloproteinase 9 (ADAM9) was a direct target of miR-590. Delivery of miR-590 mimic was found to decrease endogenous ADAM9 expression in NSCLC cells. Enforced expression of a miRNA-resistant form of ADAM9 significantly restored the aggressive behaviors in miR-590-overexpressing NSCLC cells. Taken together, our data reveal miR-590 as a tumor suppressor in NSCLC, which is at least partially mediated through targeting of ADAM9. Restoration of miR-590 may provide a promising therapeutic strategy for NSCLC.
authors: Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
authors: Fei-Fei
authors: FF
authors: Wang
authors: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
authors: Song
authors: S
authors: Wang
authors: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
authors: Wen-Hua
authors: WH
authors: Xue
authors: Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. cjr.chjl@vip.163.com.
authors: Jing-Liang
authors: JL
authors: Cheng
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C568221:MIRN590 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D051722:ADAM Proteins; C098339:ADAM9 protein, human
keywords: Cancer growth; Dysregulation; Metastasis; Target genes; microRNA