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miR-103 Promotes Proliferation and Metastasis by Targeting KLF4 in Gastric Cancer

MicroRNAs (miRNAs) play important roles in the cancer development and progression; overexpression of miR-103 has been identified in various tumors. However, its biological function and regulatory mechanism involved in modulation of human gastric cancer (GC) remain largely unknown. This study aimed t...

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Detalles Bibliográficos
Autores principales: Zheng, Jie, Liu, Yuzhen, Qiao, Yanchun, Zhang, Liying, Lu, Shijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454823/
https://www.ncbi.nlm.nih.gov/pubmed/28445396
http://dx.doi.org/10.3390/ijms18050910
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author Zheng, Jie
Liu, Yuzhen
Qiao, Yanchun
Zhang, Liying
Lu, Shijun
author_facet Zheng, Jie
Liu, Yuzhen
Qiao, Yanchun
Zhang, Liying
Lu, Shijun
author_sort Zheng, Jie
collection PubMed
description MicroRNAs (miRNAs) play important roles in the cancer development and progression; overexpression of miR-103 has been identified in various tumors. However, its biological function and regulatory mechanism involved in modulation of human gastric cancer (GC) remain largely unknown. This study aimed to confirm clinical significance of miR-103 and investigate its biological role and underlying mechanism in GC. Real-time quantitative PCR (qRT-PCR) revealed miR-103 was highly expressed in GC tissues and cell lines. miR-103 expression was correlated closely with tumor size, Lauren’s classification, and lymph node metastasis. Importantly, Kaplan-Meier analysis revealed that high expression of miR-103 was significantly associated with poor overall survival and disease-free survival of GC patients. Downregulation of miR-103 by transfecting with miR-103 inhibitor significantly suppressed cell proliferation, induced apoptosis, inhibited migration and invasion in vitro and in vivo. Furthermore, miRNA target databases and luciferase reporter assay confirmed that Krüppel-like Factor-4 (KLF4) was a direct target of miR-103 in GC, and there was a significant inverse correlation between miR-103 and KLF4 expression in GC tissues. Moreover, KLF4 downregulation could rescue miR-103’s oncogenic effect on GC cell proliferation, apoptosis, migration, and invasion. Therefore, these results suggested that miR-103 overexpression could contribute to tumor progression by suppressing KLF4, and it might serve as a promising candidate for the prognosis of GC patients.
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spelling pubmed-54548232017-06-08 miR-103 Promotes Proliferation and Metastasis by Targeting KLF4 in Gastric Cancer Zheng, Jie Liu, Yuzhen Qiao, Yanchun Zhang, Liying Lu, Shijun Int J Mol Sci Article MicroRNAs (miRNAs) play important roles in the cancer development and progression; overexpression of miR-103 has been identified in various tumors. However, its biological function and regulatory mechanism involved in modulation of human gastric cancer (GC) remain largely unknown. This study aimed to confirm clinical significance of miR-103 and investigate its biological role and underlying mechanism in GC. Real-time quantitative PCR (qRT-PCR) revealed miR-103 was highly expressed in GC tissues and cell lines. miR-103 expression was correlated closely with tumor size, Lauren’s classification, and lymph node metastasis. Importantly, Kaplan-Meier analysis revealed that high expression of miR-103 was significantly associated with poor overall survival and disease-free survival of GC patients. Downregulation of miR-103 by transfecting with miR-103 inhibitor significantly suppressed cell proliferation, induced apoptosis, inhibited migration and invasion in vitro and in vivo. Furthermore, miRNA target databases and luciferase reporter assay confirmed that Krüppel-like Factor-4 (KLF4) was a direct target of miR-103 in GC, and there was a significant inverse correlation between miR-103 and KLF4 expression in GC tissues. Moreover, KLF4 downregulation could rescue miR-103’s oncogenic effect on GC cell proliferation, apoptosis, migration, and invasion. Therefore, these results suggested that miR-103 overexpression could contribute to tumor progression by suppressing KLF4, and it might serve as a promising candidate for the prognosis of GC patients. MDPI 2017-04-26 /pmc/articles/PMC5454823/ /pubmed/28445396 http://dx.doi.org/10.3390/ijms18050910 Text en © 2017 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
Zheng, Jie
Liu, Yuzhen
Qiao, Yanchun
Zhang, Liying
Lu, Shijun
miR-103 Promotes Proliferation and Metastasis by Targeting KLF4 in Gastric Cancer
title miR-103 Promotes Proliferation and Metastasis by Targeting KLF4 in Gastric Cancer
title_full miR-103 Promotes Proliferation and Metastasis by Targeting KLF4 in Gastric Cancer
title_fullStr miR-103 Promotes Proliferation and Metastasis by Targeting KLF4 in Gastric Cancer
title_full_unstemmed miR-103 Promotes Proliferation and Metastasis by Targeting KLF4 in Gastric Cancer
title_short miR-103 Promotes Proliferation and Metastasis by Targeting KLF4 in Gastric Cancer
title_sort mir-103 promotes proliferation and metastasis by targeting klf4 in gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454823/
https://www.ncbi.nlm.nih.gov/pubmed/28445396
http://dx.doi.org/10.3390/ijms18050910
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