title: Downregulation of miR-522 suppresses proliferation and metastasis of non-small cell lung cancer cells by directly targeting DENN/MADD domain containing 2D.
abstract: Non-small cell lung cancer (NSCLC), one of the most common causes of cancer-related death, is a worldwide public health problem. MicroRNAs (miRNAs) have recently been identified as a novel class of regulators of carcinogenesis and tumor progression, including miRNAs associated with NSCLC. This study aimed to explore the role of miR-522 in NSCLC and the mechanisms underlying this role. We report here that miR-522 expression was significantly increased in both human NSCLC tissues and cell lines. Furthermore, an MTT assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay kit and flow cytometry confirmed that the inhibition of miR-522 suppressed NSCLC cells proliferation and induced apoptosis. Compared with miR-522 overexpression, miR-522 inhibitor markedly reduced cells migration and invasion, as indicated by wound-healing and transwell assays. In addition, a luciferase assay identified DENN/MADD domain containing 2D (DENND2D) as a direct target of miR-522. qRT-PCR and western blot analyses indicated the reciprocal expression of miR-522 and DENND2D in NSCLC tissue samples. DENND2D was involved in miR-522 induced proliferation and metastasis of NSCLC cells by a miRNA-masking antisense oligonucleotides (miR-mask) technology. These data highlight a novel molecular interaction between miR-522 and DENND2D, which indicates that targeting miR-522 may constitute a potential therapy for NSCLC.
authors.affiliation: Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Tianze
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.|Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ju
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Liangyu
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Zhange
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Linyou
authors.initials: L
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D034622:RNA Interference; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C582173:DENND2D protein, human; D020662:Guanine Nucleotide Exchange Factors; C560599:MIRN522 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins