Y Wang1, H Ye2, Y Yang3, J Li4, A Cen4, L Zhao3. 1. Department of Endocrinology, the First Affiliated Hospital of Jinan University, No. 613, West Huangpu Avenue, Tianhe District, Guangzhou, 510630, Guangdong Province, People's Republic of China. smeea@126.com. 2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Hepatopancreatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. 3. Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China. 4. Department of Endocrinology, the First Affiliated Hospital of Jinan University, No. 613, West Huangpu Avenue, Tianhe District, Guangzhou, 510630, Guangdong Province, People's Republic of China.
Abstract
BACKGROUND AND PURPOSE: Papillary thyroid carcinoma (PTC) is an endocrine malignancy. Increasing evidence highlights microRNAs (miRNAs) as important participants in PTC. Here, we investigated the role of miR-181a in PTC. METHODS: A microarray-based analysis was performed to identify the differential expression of miR-181a in PTC, which was validated with RT-qPCR. Protein expression of the proliferation-related factor Ki-67 and apoptosis- and migration-related factors in PTC was assessed with immunoblot analysis. A dual-luciferase reporter gene assay was adopted to verify the relationship between miR-181a and lysine demethylase 5C (KDM5C). Chromatin immunoprecipitation (ChIP) was used to detect the level of the H3K4me3 modification on S100 calcium-binding protein A2 (S100A2). Cell viability, apoptosis, and invasion and migration abilities were evaluated by Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays, respectively. The in vitro results were verified in in vivo nude mouse models. RESULTS: miR-181a was highly expressed in PTC tissues and cell lines. Silencing miR-181a repressed the proliferation and migration of PTC cells. KDM5C was identified as the target gene of miR-181a and represses S100A2 expression through histone demethylation to diminish the migration and proliferation of PTC cells. miR-181a depletion suppressed tumor growth. CONCLUSION: Collectively, these results suggest that highly expressed miR-181a promotes the proliferation of PTC cells by increasing the expression of the oncogene S100A2. This study contributes to the advancement of miR-181a-targeted therapeutics.
BACKGROUND AND PURPOSE: Papillary thyroid carcinoma (PTC) is an endocrine malignancy. Increasing evidence highlights microRNAs (miRNAs) as important participants in PTC. Here, we investigated the role of miR-181a in PTC. METHODS: A microarray-based analysis was performed to identify the differential expression of miR-181a in PTC, which was validated with RT-qPCR. Protein expression of the proliferation-related factor Ki-67 and apoptosis- and migration-related factors in PTC was assessed with immunoblot analysis. A dual-luciferase reporter gene assay was adopted to verify the relationship between miR-181a and lysine demethylase 5C (KDM5C). Chromatin immunoprecipitation (ChIP) was used to detect the level of the H3K4me3 modification on S100 calcium-binding protein A2 (S100A2). Cell viability, apoptosis, and invasion and migration abilities were evaluated by Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays, respectively. The in vitro results were verified in in vivo nude mouse models. RESULTS: miR-181a was highly expressed in PTC tissues and cell lines. Silencing miR-181a repressed the proliferation and migration of PTC cells. KDM5C was identified as the target gene of miR-181a and represses S100A2 expression through histone demethylation to diminish the migration and proliferation of PTC cells. miR-181a depletion suppressed tumor growth. CONCLUSION: Collectively, these results suggest that highly expressed miR-181a promotes the proliferation of PTC cells by increasing the expression of the oncogene S100A2. This study contributes to the advancement of miR-181a-targeted therapeutics.
Authors: Y Ito; H Yoshida; C Tomoda; T Uruno; A Miya; K Kobayashi; F Matsuzuka; K Kakudo; K Kuma; A Miyauchi Journal: Histopathology Date: 2005-05 Impact factor: 5.087