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KMT2A regulates cervical cancer cell growth through targeting VDAC1

Cervical cancer is an aggressive cutaneous malignancy, illuminating the molecular mechanisms of tumorigenesis and discovering novel therapeutic targets are urgently needed. KMT2A is a transcriptional co-activator regulating gene expression during early development and hematopoiesis, but the role of...

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Autores principales: Zhang, Changlin, Hua, Yijun, Qiu, Huijuan, Liu, Tianze, Long, Qian, Liao, Wei, Qiu, Jiehong, Wang, Nang, Chen, Miao, Shi, Dingbo, Yan, Yue, Xie, Chuanbo, Deng, Wuguo, Li, Tian, Li, Yizhuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288919/
https://www.ncbi.nlm.nih.gov/pubmed/32436862
http://dx.doi.org/10.18632/aging.103229
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author Zhang, Changlin
Hua, Yijun
Qiu, Huijuan
Liu, Tianze
Long, Qian
Liao, Wei
Qiu, Jiehong
Wang, Nang
Chen, Miao
Shi, Dingbo
Yan, Yue
Xie, Chuanbo
Deng, Wuguo
Li, Tian
Li, Yizhuo
author_facet Zhang, Changlin
Hua, Yijun
Qiu, Huijuan
Liu, Tianze
Long, Qian
Liao, Wei
Qiu, Jiehong
Wang, Nang
Chen, Miao
Shi, Dingbo
Yan, Yue
Xie, Chuanbo
Deng, Wuguo
Li, Tian
Li, Yizhuo
author_sort Zhang, Changlin
collection PubMed
description Cervical cancer is an aggressive cutaneous malignancy, illuminating the molecular mechanisms of tumorigenesis and discovering novel therapeutic targets are urgently needed. KMT2A is a transcriptional co-activator regulating gene expression during early development and hematopoiesis, but the role of KMT2A in cervical cancer remains unknown. Here, we demonstrated that KMT2A regulated cervical cancer growth via targeting VADC1. Knockdown of KMT2A significantly suppressed cell proliferation and migration and induced apoptosis in cervical cancer cells, accompanying with activation of PARP/caspase pathway and inhibition of VADC1. Overexpression of VDAC1 reversed the KMT2A knockdown-mediated regulation of cell proliferation, migration and apoptosis. The in vivo results from a cervical cancer xenograft mouse model also validated that KMT2A knockdown suppressed tumor growth by inhibiting VDAC1, whereas KMT2A overexpression promoted cervical cancer growth. Moreover, analyses of Biewenga cervix database and clinical samples showed that both KMT2A and VDAC1 were upregulated in cervix squamous cell carcinoma compared with cervix uteri tissues, and their expression was negatively correlated with the differentiation grade of cervical cancer. Our results therefore indicated that the KMT2A/VDAC1 signaling axis may be a potential new mechanism of cervical carcinogenesis.
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spelling pubmed-72889192020-06-22 KMT2A regulates cervical cancer cell growth through targeting VDAC1 Zhang, Changlin Hua, Yijun Qiu, Huijuan Liu, Tianze Long, Qian Liao, Wei Qiu, Jiehong Wang, Nang Chen, Miao Shi, Dingbo Yan, Yue Xie, Chuanbo Deng, Wuguo Li, Tian Li, Yizhuo Aging (Albany NY) Research Paper Cervical cancer is an aggressive cutaneous malignancy, illuminating the molecular mechanisms of tumorigenesis and discovering novel therapeutic targets are urgently needed. KMT2A is a transcriptional co-activator regulating gene expression during early development and hematopoiesis, but the role of KMT2A in cervical cancer remains unknown. Here, we demonstrated that KMT2A regulated cervical cancer growth via targeting VADC1. Knockdown of KMT2A significantly suppressed cell proliferation and migration and induced apoptosis in cervical cancer cells, accompanying with activation of PARP/caspase pathway and inhibition of VADC1. Overexpression of VDAC1 reversed the KMT2A knockdown-mediated regulation of cell proliferation, migration and apoptosis. The in vivo results from a cervical cancer xenograft mouse model also validated that KMT2A knockdown suppressed tumor growth by inhibiting VDAC1, whereas KMT2A overexpression promoted cervical cancer growth. Moreover, analyses of Biewenga cervix database and clinical samples showed that both KMT2A and VDAC1 were upregulated in cervix squamous cell carcinoma compared with cervix uteri tissues, and their expression was negatively correlated with the differentiation grade of cervical cancer. Our results therefore indicated that the KMT2A/VDAC1 signaling axis may be a potential new mechanism of cervical carcinogenesis. Impact Journals 2020-05-21 /pmc/articles/PMC7288919/ /pubmed/32436862 http://dx.doi.org/10.18632/aging.103229 Text en Copyright © 2020 Zhang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhang, Changlin
Hua, Yijun
Qiu, Huijuan
Liu, Tianze
Long, Qian
Liao, Wei
Qiu, Jiehong
Wang, Nang
Chen, Miao
Shi, Dingbo
Yan, Yue
Xie, Chuanbo
Deng, Wuguo
Li, Tian
Li, Yizhuo
KMT2A regulates cervical cancer cell growth through targeting VDAC1
title KMT2A regulates cervical cancer cell growth through targeting VDAC1
title_full KMT2A regulates cervical cancer cell growth through targeting VDAC1
title_fullStr KMT2A regulates cervical cancer cell growth through targeting VDAC1
title_full_unstemmed KMT2A regulates cervical cancer cell growth through targeting VDAC1
title_short KMT2A regulates cervical cancer cell growth through targeting VDAC1
title_sort kmt2a regulates cervical cancer cell growth through targeting vdac1
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288919/
https://www.ncbi.nlm.nih.gov/pubmed/32436862
http://dx.doi.org/10.18632/aging.103229
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