Journal Article

MiR-20a Is Upregulated in Anaplastic Thyroid Cancer and Targets LIMK1

Xiong, Yin, Zhang, Lisa, Kebebew, Electron

2014

Overview

There have been conflicting reports regarding the function of miR-20a in a variety of cancer types and we previously found it to be dysregulated in sporadic versus familial papillary thyroid cancer. In this study, we studied the expression of miR-20a in normal, benign and malignant thyroid samples, and its effect on thyroid cancer cells in vitro and in vivo. The expression of miR-20a in normal, benign and malignant thyroid tissue was determined by quantitative RT-PCR. Thyroid cancer cells were transfected with miR-20a and the effect on cellular proliferation, tumor spheroid formation, and invasion was evaluated. Target genes of miR-20 were determined by genome-wide mRNA expression analysis with miR-20a overexpression in thyroid cancer cells and target prediction database. Target genes were validated by quantitative PCR and immunoblotting, and luciferase assays. MiR-20a expression was significantly higher in anaplastic thyroid cancer than in differentiated thyroid cancer, and benign and normal thyroid tissues. MiR-20a significantly inhibited thyroid cancer cell proliferation in vitro (p<0.01) and in vivo (p<0.01), tumor spheroid formation (p<0.05) and invasion (p<0.05) in multiple thyroid cancer cell lines. We found that LIMK1 was a target of miR-20a in thyroid cancer cell lines and direct knockdown of LIMK1 recapitulated the effect of miR-20a in thyroid cancer cells. To our knowledge, this is the first study to demonstrate that miR-20a plays a role as a tumor suppressor in thyroid cancer cells and targets LIMK1. Our findings suggest the upregulated expression of miR-20a in anaplastic thyroid cancer counteracts thyroid cancer progression and may have therapeutic potential.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Animals / Benign / Biology and Life Sciences / Biotechnology / Breast cancer / Cancer / Cell cycle / Cell Line, Tumor / Cell Proliferation / Cell Transformation, Neoplastic / Gene expression / Genes / Genomes / Genomics / Humans / Immunoblotting / In vitro methods and tests / In vivo methods and tests / Kinases / LIM kinase / Lim Kinases - genetics / Luciferase / Medical research / Medicine and Health Sciences / Metastasis / Mice / MicroRNAs / MicroRNAs - genetics / Neoplasm Invasiveness / Oncology / Papillary thyroid cancer / Polymerase chain reaction / Prostate cancer / RNA / Spheroids, Cellular - pathology / Thyroid / Thyroid cancer / Thyroid Carcinoma, Anaplastic - genetics / Thyroid Carcinoma, Anaplastic - pathology / Thyroid Gland - cytology / Thyroid Gland - metabolism / Thyroid Gland - pathology / Tissues / Tumor cell lines / Tumor suppressor genes / Tumors / Up-Regulation