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Silencing PROK2 Inhibits Invasion of Human Cervical Cancer Cells by Targeting MMP15 Expression

Cervical cancer is the second most frequent type of gynecologic cancer worldwide. Prokineticin 2 (PROK2) is reported to be involved in tumor progression in some malignant tumors. However, the role of PROK2 in the development of cervical cancer remains unknown. Our results indicate that PROK2 is over...

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Autores principales: Wu, Min-Hua, Wu, Pei-Ru, Hsieh, Yi-Hsien, Lin, Chia-Liang, Liu, Chung-Jung, Ying, Tsung-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504693/
https://www.ncbi.nlm.nih.gov/pubmed/32887509
http://dx.doi.org/10.3390/ijms21176391
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author Wu, Min-Hua
Wu, Pei-Ru
Hsieh, Yi-Hsien
Lin, Chia-Liang
Liu, Chung-Jung
Ying, Tsung-Ho
author_facet Wu, Min-Hua
Wu, Pei-Ru
Hsieh, Yi-Hsien
Lin, Chia-Liang
Liu, Chung-Jung
Ying, Tsung-Ho
author_sort Wu, Min-Hua
collection PubMed
description Cervical cancer is the second most frequent type of gynecologic cancer worldwide. Prokineticin 2 (PROK2) is reported to be involved in tumor progression in some malignant tumors. However, the role of PROK2 in the development of cervical cancer remains unknown. Our results indicate that PROK2 is overexpressed in the human cervical cancer. Cervical cancer patients with high PROK2 expression have a shorter overall survival rate (OS) and disease-free survival rate (DFS). PROK2 acts as a potential biomarker for predicting OS and DFS of cervical cancer patients. We further show that PROK2 is important factor for oncogenic migration and invasion in human cervical cancer cells. Knockdown PROK2 significantly inhibited cell migration, invasion, and MMP15 protein expression in HeLa cells. High expression of MMP15 is confirmed in the human cervical cancer, is significantly associated with the shorter overall survival rate (OS) and is correlated with PROK2 expression. Overexpression of PROK2 using PROK2 plasmid significantly reverses the function of knockdown PROK2, and further upregulates MMP15 expression, migration and invasion of human cervical cancer cells. In conclusion, our findings are the first to demonstrate the role of PROK2 as a novel and potential biomarker for clinical use, and reveal the oncogenic functions of PROK2 as therapeutic target for cervical cancer.
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spelling pubmed-75046932020-09-26 Silencing PROK2 Inhibits Invasion of Human Cervical Cancer Cells by Targeting MMP15 Expression Wu, Min-Hua Wu, Pei-Ru Hsieh, Yi-Hsien Lin, Chia-Liang Liu, Chung-Jung Ying, Tsung-Ho Int J Mol Sci Article Cervical cancer is the second most frequent type of gynecologic cancer worldwide. Prokineticin 2 (PROK2) is reported to be involved in tumor progression in some malignant tumors. However, the role of PROK2 in the development of cervical cancer remains unknown. Our results indicate that PROK2 is overexpressed in the human cervical cancer. Cervical cancer patients with high PROK2 expression have a shorter overall survival rate (OS) and disease-free survival rate (DFS). PROK2 acts as a potential biomarker for predicting OS and DFS of cervical cancer patients. We further show that PROK2 is important factor for oncogenic migration and invasion in human cervical cancer cells. Knockdown PROK2 significantly inhibited cell migration, invasion, and MMP15 protein expression in HeLa cells. High expression of MMP15 is confirmed in the human cervical cancer, is significantly associated with the shorter overall survival rate (OS) and is correlated with PROK2 expression. Overexpression of PROK2 using PROK2 plasmid significantly reverses the function of knockdown PROK2, and further upregulates MMP15 expression, migration and invasion of human cervical cancer cells. In conclusion, our findings are the first to demonstrate the role of PROK2 as a novel and potential biomarker for clinical use, and reveal the oncogenic functions of PROK2 as therapeutic target for cervical cancer. MDPI 2020-09-02 /pmc/articles/PMC7504693/ /pubmed/32887509 http://dx.doi.org/10.3390/ijms21176391 Text en © 2020 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
Wu, Min-Hua
Wu, Pei-Ru
Hsieh, Yi-Hsien
Lin, Chia-Liang
Liu, Chung-Jung
Ying, Tsung-Ho
Silencing PROK2 Inhibits Invasion of Human Cervical Cancer Cells by Targeting MMP15 Expression
title Silencing PROK2 Inhibits Invasion of Human Cervical Cancer Cells by Targeting MMP15 Expression
title_full Silencing PROK2 Inhibits Invasion of Human Cervical Cancer Cells by Targeting MMP15 Expression
title_fullStr Silencing PROK2 Inhibits Invasion of Human Cervical Cancer Cells by Targeting MMP15 Expression
title_full_unstemmed Silencing PROK2 Inhibits Invasion of Human Cervical Cancer Cells by Targeting MMP15 Expression
title_short Silencing PROK2 Inhibits Invasion of Human Cervical Cancer Cells by Targeting MMP15 Expression
title_sort silencing prok2 inhibits invasion of human cervical cancer cells by targeting mmp15 expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504693/
https://www.ncbi.nlm.nih.gov/pubmed/32887509
http://dx.doi.org/10.3390/ijms21176391
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