title: MicroR-140-5p suppresses tumor cell migration and invasion by targeting ADAM10-mediated Notch1 signaling pathway in hypopharyngeal squamous cell carcinoma.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides that negatively regulate gene expression at the post-transcriptional level. Downexpression of miR-140-5p was reported in some human cancers, and combined with a reduction of cell migration and invasion, suggesting that miR-140-5p functions as a tumor suppressor. However, little is known about the expression and function of miR-140-5p in hypopharyngeal squamous cell carcinoma (HSCC). In this research, we found that miR-140-5p was significantly downregulated in HSCC tissues and correlated to tumor classification and lymph node metastasis. Restoration of miR-140-5p suppressed the migration and invasion of FaDu cells, and decreased the protein expression levels of ADAM10. Furthermore, the luciferase reporter assay revealed that miR-140-5p was directly bound to ADAM10 mRNA and knockdown of ADAM10 could inhibit FaDu cell migration and invasion and reduced the protein expression levels of and Notch1 intracellular domain (NICD1). Of note, knockdown of Notch1 could inhibit the migration and invasion of FaDu cells and rescued the effect of miR-140-5p inhibitor in FaDu cells. Taken together, our study demonstrates that miR-140-5p suppresses tumor migration and invasion by inhibiting ADAM10-mediated Notch1 signaling pathway and suggests that miR-140-5p could have potential therapeutic applications in HSCC.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jingwuweiqi Road, Jinan 250021, PR China.
authors.forename: Peihang
authors.initials: P
authors.lastname: Jing
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jingwuweiqi Road, Jinan 250021, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Sa
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jingwuweiqi Road, Jinan 250021, PR China.
authors.forename: Xianfang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jingwuweiqi Road, Jinan 250021, PR China.
authors.forename: Xiuxiu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jingwuweiqi Road, Jinan 250021, PR China. Electronic address: xuwhns@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000072197:ADAM10 Protein; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010610:Pharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D051881:Receptor, Notch1 / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D035683:MicroRNAs; C544302:Mirn140 microRNA, human; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human
keywords: ADAM10; Cell invasion; Cell migration; Hypopharyngeal squamous cell carcinoma(HSCC); MiR-140-5p; Notch1 signaling