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MicroRNA-196a promotes cervical cancer proliferation through the regulation of FOXO1 and p27Kip1.

ABSTRACT: The phosphoinositide 3-kinase (PI3K)/Akt signalling pathway appears to be a key regulator in cervical carcinogenesis. However, the downstream regulatory mechanism of PI3K/Akt signalling remains largely unknown.The expression of miR-196a in cervical cancer cell lines and cervical cancer tissues was examined using real-time PCR. The effects of miR-196a on PI3K/Akt signalling and cellular proliferation were evaluated by bromodeoxyuridine labelling, 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazoliumbromide, colony formation assays and luciferase assays.The expression level of miR-196a was markedly increased in cervical cancer tissues and cell lines compared with normal cervical tissue and normal cervical squamous cells. Upregulation of miR-196a was correlated with advanced tumour stage and poor overall and recurrence-free survival in cervical cancer patients. Upregulation of miR-196a enhanced G1/S-phase transition and the proliferative ability of cervical cancer cells, whereas suppression of miR-196a had the opposite effect. Using bioinformatics and biological approaches, we showed that FOXO1 and p27(Kip1), two key effectors of PI3K/Akt signalling, were direct targets of miR-196a.Our findings suggest that miR-196a has an important role in promoting human cervical cancer cell proliferation and may represent a novel therapeutic target of microRNA-mediated suppression of cell proliferation in cervical cancer.

SUBMITTER: Hou T

PROVIDER: S-EPMC3950858 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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MicroRNA-196a promotes cervical cancer proliferation through the regulation of FOXO1 and p27Kip1.

Hou T T Ou J J Zhao X X Huang X X Huang Y Y Zhang Y Y

British journal of cancer 20140114 5

<h4>Background</h4>The phosphoinositide 3-kinase (PI3K)/Akt signalling pathway appears to be a key regulator in cervical carcinogenesis. However, the downstream regulatory mechanism of PI3K/Akt signalling remains largely unknown.<h4>Methods</h4>The expression of miR-196a in cervical cancer cell lines and cervical cancer tissues was examined using real-time PCR. The effects of miR-196a on PI3K/Akt signalling and cellular proliferation were evaluated by bromodeoxyuridine labelling, 3-(4,5-Dimethyl ...[more]

PMID: 24423924

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Project description:BACKGROUND:Current evidence implicates aberrant microRNA expression patterns in human malignancies; measurement of microRNA expression may have diagnostic and prognostic applications. Roles for microRNAs in head and neck squamous cell carcinomas (HNSCC) are largely unknown. HNSCC, a smoking-related cancer, is one of the most common malignancies worldwide but reliable diagnostic and prognostic markers have not been discovered so far. Some studies have evaluated the potential use of microRNA as biomarkers with clinical application in HNSCC. METHODS:MicroRNA expression profile of oral squamous cell carcinoma samples was determined by means of DNA microarrays. We also performed gain-of-function assays for two differentially expressed microRNA using two squamous cell carcinoma cell lines and normal oral keratinocytes. The effect of the over-expression of these molecules was evaluated by means of global gene expression profiling and cell proliferation assessment. RESULTS:Altered microRNA expression was detected for a total of 72 microRNAs. Among these we found well studied molecules, such as the miR-17-92 cluster, comprising potent oncogenic microRNA, and miR-34, recently found to interact with p53. HOX-cluster embedded miR-196a/b and miR-10b were up- and down-regulated, respectively, in tumor samples. Since validated HOX gene targets for these microRNAs are not consistently deregulated in HNSCC, we performed gain-of-function experiments, in an attempt to outline their possible role. Our results suggest that both molecules interfere in cell proliferation through distinct processes, possibly targeting a small set of genes involved in cell cycle progression. CONCLUSIONS:Functional data on miRNAs in HNSCC is still scarce. Our data corroborate current literature and brings new insights into the role of microRNAs in HNSCC. We also show that miR-196a and miR-10b, not previously associated with HNSCC, may play an oncogenic role in this disease through the deregulation of cell proliferation. The study of microRNA alterations in HNSCC is an essential step to the mechanistic understanding of tumor formation and could lead to the discovery of clinically relevant biomarkers.

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MicroRNA-196a promotes cervical cancer proliferation through the regulation of FOXO1 and p27Kip1.

Publications

MicroRNA-196a promotes cervical cancer proliferation through the regulation of FOXO1 and p27Kip1.

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