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Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition
Double minute chromosomes (DMs) have important implications for cancer progression because oncogenes frequently amplified on them. We previously detected a functionally undefined gene amplified on DMs, Ribosomal L22-like1 (RPL22L1). The relationship between RPL22L1 and cancer progression is unknown....
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664398/ https://www.ncbi.nlm.nih.gov/pubmed/26618703 http://dx.doi.org/10.1371/journal.pone.0143659 |
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author | Wu, Nan Wei, Jia Wang, Yuhui Yan, Jinyan Qin, Ying Tong, Dandan Pang, Bo Sun, Donglin Sun, Haiming Yu, Yang Sun, Wenjing Meng, Xiangning Zhang, Chunyu Bai, Jing Chen, Feng Geng, Jingshu Lee, Ki-Young Fu, Songbin Jin, Yan |
author_facet | Wu, Nan Wei, Jia Wang, Yuhui Yan, Jinyan Qin, Ying Tong, Dandan Pang, Bo Sun, Donglin Sun, Haiming Yu, Yang Sun, Wenjing Meng, Xiangning Zhang, Chunyu Bai, Jing Chen, Feng Geng, Jingshu Lee, Ki-Young Fu, Songbin Jin, Yan |
author_sort | Wu, Nan |
collection | PubMed |
description | Double minute chromosomes (DMs) have important implications for cancer progression because oncogenes frequently amplified on them. We previously detected a functionally undefined gene amplified on DMs, Ribosomal L22-like1 (RPL22L1). The relationship between RPL22L1 and cancer progression is unknown. Here, RPL22L1 was characterized for its role in ovarian cancer (OC) metastasis and its underlying mechanism was examined. DNA copy number and mRNA expression of RPL22L1 in OC cells was analyzed using data obtained from The Cancer Genome Atlas and the Gene Expression Omnibus database. An immunohistochemical analysis of clinical OC specimens was performed and the relationships between expression level and clinicopathological factors were evaluated. Additionally, in vivo and in vitro assays were performed to understand the role of RPL22L1 in OC. RPL22L1 expression was higher in OC specimens than in normal tissues, and its expression level was highly positively correlated with invasion and lymph node metastasis (P < 0.05). RPL22L1 over-expression significantly enhanced intraperitoneal xenograft tumor development in nude mice and promoted invasion and migration in vitro. Additionally, RPL22L1 knockdown remarkably inhibited UACC-1598 cells invasion and migration. Further, RPL22L1 over-expression up-regulated the mesenchymal markers vimentin, fibronectin, and α-SMA, reduced expression of the epithelial markers E-cadherin, α-catenin, and β-catenin. RPL22L1 inhibition reduced expression of vimentin and N-cadherin. These results suggest that RPL22L1 induces epithelial-to-mesenchymal transition (EMT). Our data showed that the DMs amplified gene RPL22L1 is critical in maintaining the aggressive phenotype of OC and in triggering cell metastasis by inducing EMT. It could be employed as a novel prognostic marker and/or effective therapeutic target for OC. |
format | Online Article Text |
id | pubmed-4664398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-46643982015-12-10 Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition Wu, Nan Wei, Jia Wang, Yuhui Yan, Jinyan Qin, Ying Tong, Dandan Pang, Bo Sun, Donglin Sun, Haiming Yu, Yang Sun, Wenjing Meng, Xiangning Zhang, Chunyu Bai, Jing Chen, Feng Geng, Jingshu Lee, Ki-Young Fu, Songbin Jin, Yan PLoS One Research Article Double minute chromosomes (DMs) have important implications for cancer progression because oncogenes frequently amplified on them. We previously detected a functionally undefined gene amplified on DMs, Ribosomal L22-like1 (RPL22L1). The relationship between RPL22L1 and cancer progression is unknown. Here, RPL22L1 was characterized for its role in ovarian cancer (OC) metastasis and its underlying mechanism was examined. DNA copy number and mRNA expression of RPL22L1 in OC cells was analyzed using data obtained from The Cancer Genome Atlas and the Gene Expression Omnibus database. An immunohistochemical analysis of clinical OC specimens was performed and the relationships between expression level and clinicopathological factors were evaluated. Additionally, in vivo and in vitro assays were performed to understand the role of RPL22L1 in OC. RPL22L1 expression was higher in OC specimens than in normal tissues, and its expression level was highly positively correlated with invasion and lymph node metastasis (P < 0.05). RPL22L1 over-expression significantly enhanced intraperitoneal xenograft tumor development in nude mice and promoted invasion and migration in vitro. Additionally, RPL22L1 knockdown remarkably inhibited UACC-1598 cells invasion and migration. Further, RPL22L1 over-expression up-regulated the mesenchymal markers vimentin, fibronectin, and α-SMA, reduced expression of the epithelial markers E-cadherin, α-catenin, and β-catenin. RPL22L1 inhibition reduced expression of vimentin and N-cadherin. These results suggest that RPL22L1 induces epithelial-to-mesenchymal transition (EMT). Our data showed that the DMs amplified gene RPL22L1 is critical in maintaining the aggressive phenotype of OC and in triggering cell metastasis by inducing EMT. It could be employed as a novel prognostic marker and/or effective therapeutic target for OC. Public Library of Science 2015-11-30 /pmc/articles/PMC4664398/ /pubmed/26618703 http://dx.doi.org/10.1371/journal.pone.0143659 Text en © 2015 Wu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Wu, Nan Wei, Jia Wang, Yuhui Yan, Jinyan Qin, Ying Tong, Dandan Pang, Bo Sun, Donglin Sun, Haiming Yu, Yang Sun, Wenjing Meng, Xiangning Zhang, Chunyu Bai, Jing Chen, Feng Geng, Jingshu Lee, Ki-Young Fu, Songbin Jin, Yan Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition |
title | Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition |
title_full | Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition |
title_fullStr | Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition |
title_full_unstemmed | Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition |
title_short | Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition |
title_sort | ribosomal l22-like1 (rpl22l1) promotes ovarian cancer metastasis by inducing epithelial-to-mesenchymal transition |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664398/ https://www.ncbi.nlm.nih.gov/pubmed/26618703 http://dx.doi.org/10.1371/journal.pone.0143659 |
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