MiR-203 is involved in the laryngeal carcinoma pathogenesis via targeting VEGFA and Cox-2

Lin Xu,1 Bin Shen,2 Tingting Chen,3 Pin Dong2 1Department of Otolaryngology, Second Affiliated Hospital of Zhejiang University Medical College, Hangzhou, 2Department of Otolaryngology-Head& Neck Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, 3LishuiCentr...

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Published inOncoTargets and therapy Vol. 2016; no. Issue 1; pp. 4629 - 4637
Main Authors Xu L, Shen B, Chen TT, Dong P
Format Journal Article
LanguageEnglish
Published Dove Medical Press 01.07.2016
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Summary:Lin Xu,1 Bin Shen,2 Tingting Chen,3 Pin Dong2 1Department of Otolaryngology, Second Affiliated Hospital of Zhejiang University Medical College, Hangzhou, 2Department of Otolaryngology-Head& Neck Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, 3LishuiCentral Hospital, Lishui, Zhejiang Province, People's Republic of China Abstract: The development of laryngeal squamous cell carcinoma (LSCC) is a multistep process involving multiple factors. MicroRNAs, a group of important negative regulators of gene expression, have also been confirmed to be involved in the LSCC pathogenesis. In the present study, we compared the expression of nine selected microRNAs in the LSCC tissues and adjacent nontumor tissues. We found that the expression of miR-203 was significantly reduced in the LSCC tissues. Predicted by using bioinformatics tools, we found that VEGFA and cyclooxygenase-2 (Cox-2) may be direct targets of miR-203. By subsequent determination through dual-luciferase assay and Western blot, we confirmed that miR-203 suppresses the expression of VEGFA and Cox-2 by directly targeting 3'-untranslated region. Meanwhile, by analyzing the relationship between miR-203 and VEGFA in clinical tissue samples, we found that a negative correlation existed in the expression of miR-203 and VEGFA (P=0.0096, r=-0.33). Similarly, the expression of miR-203 and Cox-2 also has a negative correlation (P=0.0019, r=-0.46). Subsequently, in vitro functional study indicated that miR-203 played as a tumor suppressor by repressing proliferation, migration, and invasion of Hep-2 cells. The overexpression of VEGFA partially rescued the effect of overexpressed miR-203. Overexpressed Cox-2 partially rescued the effect of miR-203 on Hep-2 cell proliferation but not on the cell migration and invasion capacity. These findings suggest that miR-203 plays as a tumor suppressor in LSCC, partially by regulating VEGFA and Cox-2, and may serve as a potential target for therapeutic intervention. Keywords: non-coding RNA, laryngeal squamous cell carcinoma, correlation analysis
ISSN:1178-6930
1178-6930