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

Autor: Qian Zhou, Juan Guo, Wenjie Huang, Xiaosi Yu, Chen Xu, Xinghua Long
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Molecular Oncology, Vol 14, Iss 9, Pp 2231-2250 (2020)
Druh dokumentu: article
ISSN: 1878-0261
1574-7891
DOI: 10.1002/1878-0261.12700
Popis: 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.
Databáze: Directory of Open Access Journals
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