Cargando…

miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer

Epithelial ovarian carcinoma (EOC) is the most lethal gynecologic malignancy. However, the molecular mechanisms remain unclear. In this study, we found that miR-146b was downregulated in EOC and its expression level was negatively correlated with the pathological staging. Follow-up functional experi...

Descripción completa

Detalles Bibliográficos
Autores principales: Yan, Meina, Yang, Xinxin, Shen, Rong, Wu, Chengjiang, Wang, Hui, Ye, Qing, Yang, Peifang, Zhang, Lubin, Chen, Miao, Wan, Bing, Zhang, Qinqin, Xia, Sheng, Lu, Xiaodong, Shao, Genbao, Zhou, Xiaoming, Yu, Jun, Shao, Qixiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224598/
https://www.ncbi.nlm.nih.gov/pubmed/30409964
http://dx.doi.org/10.1038/s41419-018-1093-9
_version_ 1783369629626793984
author Yan, Meina
Yang, Xinxin
Shen, Rong
Wu, Chengjiang
Wang, Hui
Ye, Qing
Yang, Peifang
Zhang, Lubin
Chen, Miao
Wan, Bing
Zhang, Qinqin
Xia, Sheng
Lu, Xiaodong
Shao, Genbao
Zhou, Xiaoming
Yu, Jun
Shao, Qixiang
author_facet Yan, Meina
Yang, Xinxin
Shen, Rong
Wu, Chengjiang
Wang, Hui
Ye, Qing
Yang, Peifang
Zhang, Lubin
Chen, Miao
Wan, Bing
Zhang, Qinqin
Xia, Sheng
Lu, Xiaodong
Shao, Genbao
Zhou, Xiaoming
Yu, Jun
Shao, Qixiang
author_sort Yan, Meina
collection PubMed
description Epithelial ovarian carcinoma (EOC) is the most lethal gynecologic malignancy. However, the molecular mechanisms remain unclear. In this study, we found that miR-146b was downregulated in EOC and its expression level was negatively correlated with the pathological staging. Follow-up functional experiments illustrated that overexpression of miR-146b significantly inhibited cell migration and invasion, and increased cell proliferation, but it also improved the response to chemotherapeutic agents. Mechanistically, we demonstrated that miR-146b exerted its function mainly through inhibiting F-box and leucine-rich repeat protein 10 (FBXL10), and upregulated the Cyclin D1, vimentin (VIM), and zona-occludens-1 (ZO-1) expression in EOC. These findings indicate that miR-146b–FBXL10 axis is an important epigenetic regulation pathway in EOC. Low miR-146b may contribute to cancer progression from primary stage to advanced stage, and may be the promising therapeutic target of EOC.
format Online
Article
Text
id pubmed-6224598
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-62245982018-11-09 miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer Yan, Meina Yang, Xinxin Shen, Rong Wu, Chengjiang Wang, Hui Ye, Qing Yang, Peifang Zhang, Lubin Chen, Miao Wan, Bing Zhang, Qinqin Xia, Sheng Lu, Xiaodong Shao, Genbao Zhou, Xiaoming Yu, Jun Shao, Qixiang Cell Death Dis Article Epithelial ovarian carcinoma (EOC) is the most lethal gynecologic malignancy. However, the molecular mechanisms remain unclear. In this study, we found that miR-146b was downregulated in EOC and its expression level was negatively correlated with the pathological staging. Follow-up functional experiments illustrated that overexpression of miR-146b significantly inhibited cell migration and invasion, and increased cell proliferation, but it also improved the response to chemotherapeutic agents. Mechanistically, we demonstrated that miR-146b exerted its function mainly through inhibiting F-box and leucine-rich repeat protein 10 (FBXL10), and upregulated the Cyclin D1, vimentin (VIM), and zona-occludens-1 (ZO-1) expression in EOC. These findings indicate that miR-146b–FBXL10 axis is an important epigenetic regulation pathway in EOC. Low miR-146b may contribute to cancer progression from primary stage to advanced stage, and may be the promising therapeutic target of EOC. Nature Publishing Group UK 2018-11-08 /pmc/articles/PMC6224598/ /pubmed/30409964 http://dx.doi.org/10.1038/s41419-018-1093-9 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yan, Meina
Yang, Xinxin
Shen, Rong
Wu, Chengjiang
Wang, Hui
Ye, Qing
Yang, Peifang
Zhang, Lubin
Chen, Miao
Wan, Bing
Zhang, Qinqin
Xia, Sheng
Lu, Xiaodong
Shao, Genbao
Zhou, Xiaoming
Yu, Jun
Shao, Qixiang
miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer
title miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer
title_full miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer
title_fullStr miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer
title_full_unstemmed miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer
title_short miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer
title_sort mir-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via fbxl10 in ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224598/
https://www.ncbi.nlm.nih.gov/pubmed/30409964
http://dx.doi.org/10.1038/s41419-018-1093-9
work_keys_str_mv AT yanmeina mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT yangxinxin mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT shenrong mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT wuchengjiang mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT wanghui mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT yeqing mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT yangpeifang mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT zhanglubin mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT chenmiao mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT wanbing mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT zhangqinqin mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT xiasheng mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT luxiaodong mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT shaogenbao mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT zhouxiaoming mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT yujun mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer
AT shaoqixiang mir146bpromotescellproliferationandincreaseschemosensitivitybutattenuatescellmigrationandinvasionviafbxl10inovariancancer