title: Downregulation of miR-34a contributes to the proliferation and migration of laryngeal carcinoma cells by targeting cyclin D1.
abstract: Laryngeal carcinoma is one of the most common head and neck cancers. MicroRNAs are a class of small non-coding RNAs 18-25 nucleotides in length that post-transcriptionally regulate gene expression and have a pivotal role in many biological processes including cancer development. In this study, we investigated the role of miR-34a in laryngeal carcinoma and confirmed the regulation of cyclin D1 (CCND1) by miR-34a. We examined miR-34a expression levels in 71 laryngeal carcinoma patient specimens by quantitative reverse transcription-PCR, and analyzed the clinicopathological significance of the obtained data. Then, functional assays were performed to investigate the potential effects of miR-34a on cancer cell proliferation and migration. In addition, western blotting, luciferase reporter assay and several algorithms were conducted to confirm that CCND1 is directly regulated by miR-34a. We demonstrated that the miR-34a expression level was significantly downregulated in laryngeal carcinoma clinical specimens compared with that observed in their paired adjacent normal tissues. Additionally, miR-34a expression was also inversely correlated with lymph node metastasis and clinical stage. Functional assays showed that ectopic expression of miR-34a inhibited cell proliferation and migration in laryngeal carcinoma cells. Bioinformatic analysis identified CCND1 as a potential target of miR-34a. Moreover, we confirmed that miR-34a inhibited the expression of CCND1 by directly binding to its 3'-untranslated region. Silencing of CCND1 induced effects similar to those of miR-34a ectopic expression, and in laryngeal carcinoma tissues, miR-34a and CCND1 were inversely correlated. Our data suggest that tumor suppressor miR-34a could serve as a new potential diagnostic marker and that ectopic expression of miR-34a may be used as a therapeutic target for laryngeal carcinoma.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Laisheng
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Pinning
authors.initials: P
authors.lastname: Feng
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Jingjia
authors.initials: J
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1