Abstract

BackgroundVarious microRNAs (miRNAs) negatively modulate genes that are involved in cellular proliferation, differentiation, invasion, and apoptosis. In many types of cancer, the expression profiles of these miRNAs are altered. Recently, miR-101 was identified as a tumour suppressor and was found to be expressed at low levels in various types of tumours, including prostate, breast, endometrium, and bladder cancers. However, the function(s) of miR-101 in laryngeal carcinoma remain unknown.MethodsThe expression levels of miR-101 in laryngeal squamous cell carcinoma (LSCC) tissues and cells were detected by qPCR. Cell proliferation, migration, cell cycle, and apoptosis assay were applied to assess the function(s) of miR-101 in vitro. Nude mice subcutaneous tumour model was used to perform in vivo study. Moreover, we identified Cyclin-dependent kinase 8 (CDK8) as the target of miR-101 by a luciferase assay. The possible downstream effectors of CDK8 were investigated in Wnt/β-catenin signaling pathway. Changes of CDK8, β-catenin, and cyclin D1 protein levels were analyzed by western blotting and immunohistochemical staining. The prognostic effect of miR-101 was evaluated using the Kaplan–Meier method.ResultsExpression of miR-101 was down-regulated in the LSCC tissues compared with the adjacent normal tissues. Furthermore, downregulation of miR-101 correlated with T3–4 tumour grade, lymph node metastasis, and an advanced clinical stage in the LSCC patients examined (P < 0.05). The low level of miR-101 expression was associated with poor prognosis (P < 0.05). CDK8 was identified as the target gene of miR-101 by luciferase reporter assay. Moreover, we showed that up-regulation of miR-101 expression suppressed humen LSCC Hep-2 cells proliferation and migration, and induced cell-cycle arrest. Increased expression of miR-101 induced cells apoptosis both in vitro and in vivo. Correspondingly, exogenous expression of miR-101 significantly reduced the growth of tumour in a LSCC xenograft model. Furthermore, the miR-101 level was inversely correlated with levels of CDK8, β-catenin, and cyclin D1 in western blotting assay and immunohistochemical staining assay.ConclusionsThese results indicate that miR-101 is a potent tumour repressor that directly represses CDK8 expression. Thus, detection and targeting of miR-101 may represent a novel diagnostic and therapeutic strategy for LSCC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0626-6) contains supplementary material, which is available to authorized users.

Highlights

  • Various microRNAs negatively modulate genes that are involved in cellular proliferation, differentiation, invasion, and apoptosis

  • The purpose of this study is to explore the role of miR101 in laryngeal squamous cell carcinoma (LSCC) cell proliferation, invasion, apoptosis and cell cycle regulation

  • Higher level of miR-101 was detected in the 16HBE cell line compared with the human LSCC cell line, Hep-2 (P < 0.05) (Fig. 1b)

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Summary

Introduction

Various microRNAs (miRNAs) negatively modulate genes that are involved in cellular proliferation, differentiation, invasion, and apoptosis. In many types of cancer, the expression profiles of these miRNAs are altered. MiR-101 was identified as a tumour suppressor and was found to be expressed at low levels in various types of tumours, including prostate, breast, endometrium, and bladder cancers. The function(s) of miR-101 in laryngeal carcinoma remain unknown. Laryngeal malignancies are the second most common cancers of the head and neck, and more than 95 % of cases worldwide are diagnosed as laryngeal squamous cell carcinoma (LSCC) [1,2,3]. According to the American Cancer Society, 12,720 new cases and 3,600 deaths due to LSCC were estimated for the United States in 2010 [4]. Treatments for cancer of the larynx include surgery, radiotherapy, chemotherapy, or a comprehensive therapy approach. Most patients diagnosed with advanced-stage laryngeal cancer die of recurrence and/or metastasis. A better understanding of the molecular mechanisms involved in the carcinogenesis of LSCC would facilitate the development of much needed targeted therapies

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