title: MiR-145, a microRNA targeting ADAM17, inhibits the invasion and migration of nasopharyngeal carcinoma cells.
abstract: MiR-145 is downregulated and functions as a tumor suppressor in many malignancies. In this study, the biological function, molecular mechanism, and direct target genes of miR-145 in nasopharyngeal carcinoma (NPC) cells were investigated. Cell survival was detected by cell viability assay, and cell cycle was determined through flow cytometry. Invasion and migration of NPC cells were examined using cell invasion and wound healing assays, respectively. A disintegrin and metalloproteinase 17 (ADAM17) was verified as the target of miR-145 through luciferase reporter assay, qRT-PCR, and Western blot analysis. In NPC cell lines, miR-145 expression was significantly downregulated and ADAM17 protein expression was upregulated. ADAM17 was downregulated at the post-transcriptional level by miR-145 via the binding site of ADAM17-3'UTR. Transfection with miR-145 mimic suppressed cell growth and induced cell cycle arrest in the G0/G1 phase by upregulating key G0/G1 phase regulators, namely, p53 and p21. MiR-145 also inhibited cellular migration and invasion through targeting ADAM17 involving the regulation of EGFR and E-cadherin. Knockdown of ADAM17 elicited similar effects to that of miR-145 on NPC cells. This study reveals that miR-145 suppressed the invasion and migration of NPC cells by targeting ADAM17. Thus, miR-145 could be a therapeutic target for NPC.
authors: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China.
authors: Jing
authors: J
authors: Wu
authors: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China.
authors: Li
authors: L
authors: Yin
authors: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China.
authors: Ning
authors: N
authors: Jiang
authors: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China.
authors: Wen-Jie
authors: WJ
authors: Guo
authors: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China.
authors: Jia-Jia
authors: JJ
authors: Gu
authors: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China.
authors: Meng
authors: M
authors: Chen
authors: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China.
authors: You-You
authors: YY
authors: Xia
authors: Research Center of Clinical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China.
authors: Jian-Zhong
authors: JZ
authors: Wu
authors: Research Center of Clinical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China.
authors: Dan
authors: D
authors: Chen
authors: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China.
authors: Jian-Feng
authors: JF
authors: Wu
authors: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China.
authors: De-Jun
authors: DJ
authors: Wang
authors: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China.
authors: Dan
authors: D
authors: Zong
authors: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China.
authors: Nan
authors: N
authors: Zhang
authors: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China.
authors: Kai
authors: K
authors: Ding
authors: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China.
authors: Teng
authors: T
authors: Huang
authors: Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, 42 Bai Zi Ting Road, Nanjing, Jiangsu 210000, China. Electronic address: hexiadoctor@163.com.
authors: Xia
authors: X
authors: He
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D051722:ADAM Proteins / Q000235:genetics*; D000072198:ADAM17 Protein; D015820:Cadherins / Q000235:genetics; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D015820:Cadherins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; C512478:EGFR protein, human; D066246:ErbB Receptors; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
keywords: ADAM17; Invasion; MiR-145; Migration; Nasopharyngeal carcinoma