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Linc‐ROR promotes the progression of breast cancer and decreases the sensitivity to rapamycin through miR‐194‐3p targeting MECP2

linc‐ROR is reported to be a potential biomarker of breast cancer, but the detailed mechanism of linc‐ROR‐mediated breast cancer regulation has not been fully studied. We aimed to explore how linc‐ROR affects proliferation, metastasis, and drug sensitivity in breast cancer. Cell lines in which linc‐...

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Detalles Bibliográficos
Autores principales: Zhou, Qian, Guo, Juan, Huang, Wenjie, Yu, Xiaosi, Xu, Chen, Long, Xinghua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463371/
https://www.ncbi.nlm.nih.gov/pubmed/32335998
http://dx.doi.org/10.1002/1878-0261.12700
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author Zhou, Qian
Guo, Juan
Huang, Wenjie
Yu, Xiaosi
Xu, Chen
Long, Xinghua
author_facet Zhou, Qian
Guo, Juan
Huang, Wenjie
Yu, Xiaosi
Xu, Chen
Long, Xinghua
author_sort Zhou, Qian
collection PubMed
description linc‐ROR is reported to be a potential biomarker of breast cancer, but the detailed mechanism of linc‐ROR‐mediated breast cancer regulation has not been fully studied. We aimed to explore how linc‐ROR affects proliferation, metastasis, and drug sensitivity in breast cancer. Cell lines in which linc‐ROR was overexpressed or knocked down were constructed, and the cell proliferation, colony formation, cell migration, and invasion abilities of these lines were explored. A CCK‐8 assay was performed to determine the sensitivity of the breast cancer cells to rapamycin. Next‐generation sequencing was conducted to explore the detailed regulatory mechanism of linc‐ROR; differentially expressed RNAs in the linc‐ROR‐overexpressing cell line compared with the negative control were screened out, and their target genes were chosen to perform Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, protein–protein interaction network analysis, and competing endogenous RNA (ceRNA) network analysis. The ceRNA mechanism of linc‐ROR for miR‐194‐3p, which targets MECP2, was determined through dual‐luciferase reporter assay, RT–qPCR, western blot, and rescue experiments. Finally, we found that linc‐ROR was upregulated in breast tumor tissues. linc‐ROR promoted the cell proliferation, colony formation, cell migration, and invasion of breast cancer and decreased the sensitivity of breast cancer cells to rapamycin. The overexpression of linc‐ROR triggered changes in the whole transcriptome of breast cancer cells, and a total of 85 lncRNAs, 414 microRNAs, 490 mRNAs, and 92 circRNAs were differentially expressed in the linc‐ROR‐overexpressing cell line compared with the negative control. Through a series of bioinformatic analyses, the ‘linc‐ROR/miR‐194‐3p/MECP2’ ceRNA regulatory axis was confirmed to be involved in the linc‐ROR‐mediated progression and drug sensitivity of breast cancer. In conclusion, linc‐ROR serves as an onco‐lncRNA in breast cancer and promotes the survival of breast cancer cells during rapamycin treatment by functioning as a ceRNA sponge for miR‐194‐3p, which targets MECP2.
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spelling pubmed-74633712020-09-08 Linc‐ROR promotes the progression of breast cancer and decreases the sensitivity to rapamycin through miR‐194‐3p targeting MECP2 Zhou, Qian Guo, Juan Huang, Wenjie Yu, Xiaosi Xu, Chen Long, Xinghua Mol Oncol Research Articles linc‐ROR is reported to be a potential biomarker of breast cancer, but the detailed mechanism of linc‐ROR‐mediated breast cancer regulation has not been fully studied. We aimed to explore how linc‐ROR affects proliferation, metastasis, and drug sensitivity in breast cancer. Cell lines in which linc‐ROR was overexpressed or knocked down were constructed, and the cell proliferation, colony formation, cell migration, and invasion abilities of these lines were explored. A CCK‐8 assay was performed to determine the sensitivity of the breast cancer cells to rapamycin. Next‐generation sequencing was conducted to explore the detailed regulatory mechanism of linc‐ROR; differentially expressed RNAs in the linc‐ROR‐overexpressing cell line compared with the negative control were screened out, and their target genes were chosen to perform Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, protein–protein interaction network analysis, and competing endogenous RNA (ceRNA) network analysis. The ceRNA mechanism of linc‐ROR for miR‐194‐3p, which targets MECP2, was determined through dual‐luciferase reporter assay, RT–qPCR, western blot, and rescue experiments. Finally, we found that linc‐ROR was upregulated in breast tumor tissues. linc‐ROR promoted the cell proliferation, colony formation, cell migration, and invasion of breast cancer and decreased the sensitivity of breast cancer cells to rapamycin. The overexpression of linc‐ROR triggered changes in the whole transcriptome of breast cancer cells, and a total of 85 lncRNAs, 414 microRNAs, 490 mRNAs, and 92 circRNAs were differentially expressed in the linc‐ROR‐overexpressing cell line compared with the negative control. Through a series of bioinformatic analyses, the ‘linc‐ROR/miR‐194‐3p/MECP2’ ceRNA regulatory axis was confirmed to be involved in the linc‐ROR‐mediated progression and drug sensitivity of breast cancer. In conclusion, linc‐ROR serves as an onco‐lncRNA in breast cancer and promotes the survival of breast cancer cells during rapamycin treatment by functioning as a ceRNA sponge for miR‐194‐3p, which targets MECP2. John Wiley and Sons Inc. 2020-05-24 2020-09 /pmc/articles/PMC7463371/ /pubmed/32335998 http://dx.doi.org/10.1002/1878-0261.12700 Text en © 2020 The Authors. Published by FEBS Press and 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 Research Articles
Zhou, Qian
Guo, Juan
Huang, Wenjie
Yu, Xiaosi
Xu, Chen
Long, Xinghua
Linc‐ROR promotes the progression of breast cancer and decreases the sensitivity to rapamycin through miR‐194‐3p targeting MECP2
title Linc‐ROR promotes the progression of breast cancer and decreases the sensitivity to rapamycin through miR‐194‐3p targeting MECP2
title_full Linc‐ROR promotes the progression of breast cancer and decreases the sensitivity to rapamycin through miR‐194‐3p targeting MECP2
title_fullStr Linc‐ROR promotes the progression of breast cancer and decreases the sensitivity to rapamycin through miR‐194‐3p targeting MECP2
title_full_unstemmed Linc‐ROR promotes the progression of breast cancer and decreases the sensitivity to rapamycin through miR‐194‐3p targeting MECP2
title_short Linc‐ROR promotes the progression of breast cancer and decreases the sensitivity to rapamycin through miR‐194‐3p targeting MECP2
title_sort linc‐ror promotes the progression of breast cancer and decreases the sensitivity to rapamycin through mir‐194‐3p targeting mecp2
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463371/
https://www.ncbi.nlm.nih.gov/pubmed/32335998
http://dx.doi.org/10.1002/1878-0261.12700
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