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miR-1246 Targets CCNG2 to Enhance Cancer Stemness and Chemoresistance in Oral Carcinomas

MiRNAs have been recognized as crucial components in carcinogenesis, but whether miR-1246 affects the cancer stemness and drug resistance in oral squamous cell carcinoma (OSCC) has not been fully understood and its downstream targets still need to be unraveled. In the present work, we employed miRNA...

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Autores principales: Lin, Shih-Shen, Peng, Chih-Yu, Liao, Yi-Wen, Chou, Ming-Yung, Hsieh, Pei-Ling, Yu, Cheng-Chia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115994/
https://www.ncbi.nlm.nih.gov/pubmed/30115848
http://dx.doi.org/10.3390/cancers10080272
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author Lin, Shih-Shen
Peng, Chih-Yu
Liao, Yi-Wen
Chou, Ming-Yung
Hsieh, Pei-Ling
Yu, Cheng-Chia
author_facet Lin, Shih-Shen
Peng, Chih-Yu
Liao, Yi-Wen
Chou, Ming-Yung
Hsieh, Pei-Ling
Yu, Cheng-Chia
author_sort Lin, Shih-Shen
collection PubMed
description MiRNAs have been recognized as crucial components in carcinogenesis, but whether miR-1246 affects the cancer stemness and drug resistance in oral squamous cell carcinoma (OSCC) has not been fully understood and its downstream targets still need to be unraveled. In the present work, we employed miRNAs RT-PCR analysis to evaluate the expression of miR-1246 in tumor tissues and oral cancer stem cells (OCSC). Stemness phenotypes, including self-renewal, migration, invasion, colony formation capacities, and in vivo oncogenicity of oral cancer cells following transfected with miR-1246 inhibitors or mimics were examined. Our results suggested that the expression level of miR-1246 was significantly upregulated in the tumor tissues and OCSC. Kaplan-Meier survival analysis of OSCC patients with high levels of miR-1246 had the worst survival rate compared to their low-expression counterparts. Inhibition of miR-1246 in OCSC significantly reduced the stemness hallmarks, while overexpression of miR-1246 enhanced these characteristics. Moreover, we showed that downregulation of miR-1246 decreased chemoresistance. In addition, we verified that miR-1246-inhibited CCNG2 contributed to the cancer stemness of OSCC. These results demonstrated the significance of miR-1246 in the regulation of OSCC stemness. Targeting miR-1246-CCNG2 axis may be beneficial to suppress cancer relapse and metastasis in OSCC patients.
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spelling pubmed-61159942018-08-31 miR-1246 Targets CCNG2 to Enhance Cancer Stemness and Chemoresistance in Oral Carcinomas Lin, Shih-Shen Peng, Chih-Yu Liao, Yi-Wen Chou, Ming-Yung Hsieh, Pei-Ling Yu, Cheng-Chia Cancers (Basel) Article MiRNAs have been recognized as crucial components in carcinogenesis, but whether miR-1246 affects the cancer stemness and drug resistance in oral squamous cell carcinoma (OSCC) has not been fully understood and its downstream targets still need to be unraveled. In the present work, we employed miRNAs RT-PCR analysis to evaluate the expression of miR-1246 in tumor tissues and oral cancer stem cells (OCSC). Stemness phenotypes, including self-renewal, migration, invasion, colony formation capacities, and in vivo oncogenicity of oral cancer cells following transfected with miR-1246 inhibitors or mimics were examined. Our results suggested that the expression level of miR-1246 was significantly upregulated in the tumor tissues and OCSC. Kaplan-Meier survival analysis of OSCC patients with high levels of miR-1246 had the worst survival rate compared to their low-expression counterparts. Inhibition of miR-1246 in OCSC significantly reduced the stemness hallmarks, while overexpression of miR-1246 enhanced these characteristics. Moreover, we showed that downregulation of miR-1246 decreased chemoresistance. In addition, we verified that miR-1246-inhibited CCNG2 contributed to the cancer stemness of OSCC. These results demonstrated the significance of miR-1246 in the regulation of OSCC stemness. Targeting miR-1246-CCNG2 axis may be beneficial to suppress cancer relapse and metastasis in OSCC patients. MDPI 2018-08-16 /pmc/articles/PMC6115994/ /pubmed/30115848 http://dx.doi.org/10.3390/cancers10080272 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lin, Shih-Shen
Peng, Chih-Yu
Liao, Yi-Wen
Chou, Ming-Yung
Hsieh, Pei-Ling
Yu, Cheng-Chia
miR-1246 Targets CCNG2 to Enhance Cancer Stemness and Chemoresistance in Oral Carcinomas
title miR-1246 Targets CCNG2 to Enhance Cancer Stemness and Chemoresistance in Oral Carcinomas
title_full miR-1246 Targets CCNG2 to Enhance Cancer Stemness and Chemoresistance in Oral Carcinomas
title_fullStr miR-1246 Targets CCNG2 to Enhance Cancer Stemness and Chemoresistance in Oral Carcinomas
title_full_unstemmed miR-1246 Targets CCNG2 to Enhance Cancer Stemness and Chemoresistance in Oral Carcinomas
title_short miR-1246 Targets CCNG2 to Enhance Cancer Stemness and Chemoresistance in Oral Carcinomas
title_sort mir-1246 targets ccng2 to enhance cancer stemness and chemoresistance in oral carcinomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115994/
https://www.ncbi.nlm.nih.gov/pubmed/30115848
http://dx.doi.org/10.3390/cancers10080272
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