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Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target of cervical cancer

Maternal embryo leucine zipper kinase (MELK) is highly expressed in a variety of malignant tumors and involved in cell cycle regulation, cell proliferation, apoptosis, tumor formation etc However, the biological effects of MELK in cervical cancer are still uninvestigated. This study aimed to explore...

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Autores principales: Wang, Juan, Wang, Yamei, Shen, Fangrong, Xu, Yanting, Zhang, Yinghui, Zou, Xinwei, Zhou, Jinhua, Chen, Youguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246930/
https://www.ncbi.nlm.nih.gov/pubmed/30334367
http://dx.doi.org/10.1002/cam4.1816
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author Wang, Juan
Wang, Yamei
Shen, Fangrong
Xu, Yanting
Zhang, Yinghui
Zou, Xinwei
Zhou, Jinhua
Chen, Youguo
author_facet Wang, Juan
Wang, Yamei
Shen, Fangrong
Xu, Yanting
Zhang, Yinghui
Zou, Xinwei
Zhou, Jinhua
Chen, Youguo
author_sort Wang, Juan
collection PubMed
description Maternal embryo leucine zipper kinase (MELK) is highly expressed in a variety of malignant tumors and involved in cell cycle regulation, cell proliferation, apoptosis, tumor formation etc However, the biological effects of MELK in cervical cancer are still uninvestigated. This study aimed to explore the expression of MELK in cervical cancer, as well as its effects on the proliferation, apoptosis, DNA damage repair on cervical cancer cell line in vitro and to provide novel ideas for further improving the clinical efficacy of cervical cancer. Immunohistochemistry, Western blot, RT‐qPCR, CCK8, and immunofluorescence techniques were used to detect the expression of MELK in cervical cancer tissues, paracancerous tissues, and cervical cancer cell lines. Several cervical cancer cell lines were treated with MELK knockdown by siRNA and MELK selective inhibitor OTSSP167. The effects on proliferation, apoptosis, and colony formation capacity, and tumor cell DNA damage repair‐related factor were detected in cell lines. Our data showed that the high expression rate of MELK in cervical cancer patients was 56.92%. MELK expression in cervical cancer samples was significantly higher than that in paraneoplastic tissues. Highly expressed MELK correlated with the cervical histopathological grading and greatly increased with the cervical histopathological grading, from normal cervix and cervical intraepithelial neoplasia to cervical cancer. Moreover, the abnormal expression of MELK was related to cervical cancer metastasis at early stage. The knockdown of MELK with siRNA and OTSSP167 had strong inhibition effects on the proliferation, apoptosis, and colony formation of cervical cancer cells. MELK knockdown could also aggravate the DNA damage of cervical cancer cells possibly by homologous recombination repair pathway. Therefore, MELK may be a predicting marker of poor prognosis of cervical cancer and may also be a new therapeutic target for cervical cancer, providing ideas for improving the therapeutic effect of cervical cancer.
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spelling pubmed-62469302018-11-26 Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target of cervical cancer Wang, Juan Wang, Yamei Shen, Fangrong Xu, Yanting Zhang, Yinghui Zou, Xinwei Zhou, Jinhua Chen, Youguo Cancer Med Cancer Biology Maternal embryo leucine zipper kinase (MELK) is highly expressed in a variety of malignant tumors and involved in cell cycle regulation, cell proliferation, apoptosis, tumor formation etc However, the biological effects of MELK in cervical cancer are still uninvestigated. This study aimed to explore the expression of MELK in cervical cancer, as well as its effects on the proliferation, apoptosis, DNA damage repair on cervical cancer cell line in vitro and to provide novel ideas for further improving the clinical efficacy of cervical cancer. Immunohistochemistry, Western blot, RT‐qPCR, CCK8, and immunofluorescence techniques were used to detect the expression of MELK in cervical cancer tissues, paracancerous tissues, and cervical cancer cell lines. Several cervical cancer cell lines were treated with MELK knockdown by siRNA and MELK selective inhibitor OTSSP167. The effects on proliferation, apoptosis, and colony formation capacity, and tumor cell DNA damage repair‐related factor were detected in cell lines. Our data showed that the high expression rate of MELK in cervical cancer patients was 56.92%. MELK expression in cervical cancer samples was significantly higher than that in paraneoplastic tissues. Highly expressed MELK correlated with the cervical histopathological grading and greatly increased with the cervical histopathological grading, from normal cervix and cervical intraepithelial neoplasia to cervical cancer. Moreover, the abnormal expression of MELK was related to cervical cancer metastasis at early stage. The knockdown of MELK with siRNA and OTSSP167 had strong inhibition effects on the proliferation, apoptosis, and colony formation of cervical cancer cells. MELK knockdown could also aggravate the DNA damage of cervical cancer cells possibly by homologous recombination repair pathway. Therefore, MELK may be a predicting marker of poor prognosis of cervical cancer and may also be a new therapeutic target for cervical cancer, providing ideas for improving the therapeutic effect of cervical cancer. John Wiley and Sons Inc. 2018-10-18 /pmc/articles/PMC6246930/ /pubmed/30334367 http://dx.doi.org/10.1002/cam4.1816 Text en © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Wang, Juan
Wang, Yamei
Shen, Fangrong
Xu, Yanting
Zhang, Yinghui
Zou, Xinwei
Zhou, Jinhua
Chen, Youguo
Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target of cervical cancer
title Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target of cervical cancer
title_full Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target of cervical cancer
title_fullStr Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target of cervical cancer
title_full_unstemmed Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target of cervical cancer
title_short Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target of cervical cancer
title_sort maternal embryonic leucine zipper kinase: a novel biomarker and a potential therapeutic target of cervical cancer
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246930/
https://www.ncbi.nlm.nih.gov/pubmed/30334367
http://dx.doi.org/10.1002/cam4.1816
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