The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p

BACKGROUND: Non-small cell lung carcinomas (NSCLC) are prevalent, lethal cancers with especially grim prospects due to late-stage detection and chemoresistance. Circular RNAs (circRNAs) are non-coding RNAs that participate in tumor development. However, the role of circRNAs in NSCLC is not well know...

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Autores principales: Wei, Siliang, Zheng, Yuanyuan, Jiang, Yanru, Li, Xiaojun, Geng, Jian, Shen, Yuanbing, Li, Qin, Wang, Xiaojing, Zhao, Chengling, Chen, Yuqing, Qian, Zhongqing, Zhou, Jihong, Li, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604667/
https://www.ncbi.nlm.nih.gov/pubmed/31160270
http://dx.doi.org/10.1016/j.ebiom.2019.05.032
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author Wei, Siliang
Zheng, Yuanyuan
Jiang, Yanru
Li, Xiaojun
Geng, Jian
Shen, Yuanbing
Li, Qin
Wang, Xiaojing
Zhao, Chengling
Chen, Yuqing
Qian, Zhongqing
Zhou, Jihong
Li, Wei
author_facet Wei, Siliang
Zheng, Yuanyuan
Jiang, Yanru
Li, Xiaojun
Geng, Jian
Shen, Yuanbing
Li, Qin
Wang, Xiaojing
Zhao, Chengling
Chen, Yuqing
Qian, Zhongqing
Zhou, Jihong
Li, Wei
author_sort Wei, Siliang
collection PubMed
description BACKGROUND: Non-small cell lung carcinomas (NSCLC) are prevalent, lethal cancers with especially grim prospects due to late-stage detection and chemoresistance. Circular RNAs (circRNAs) are non-coding RNAs that participate in tumor development. However, the role of circRNAs in NSCLC is not well known. This study investigated the role of one circRNA – circPTPRA– in NSCLC and characterized its molecular mechanism of action. METHODS: circPTPRA expression was analyzed in human NSCLC tumors and matched healthy lung tissue. We performed functional characterization in NSCLC cell lines and a mouse xenograft model of NSCLC to elucidate the molecular role of circPTPRA in epithelial-mesenchymal transitioning (EMT). We also assessed the regulatory action of circPTPRA on the microRNA miR-96-5p and its target the tumor suppressor Ras association domain-containing protein 8 (RASSF8). FINDINGS: circPTPRA was significantly downregulated in NSCLC tumors relative to matched healthy lung tissue. Lower circPTPRA levels correlated with metastasis and inferior survival outcomes in NSCLC patients. circPTPRA suppressed EMT in NSCLC cell lines and reduced metastasis in the murine xenograft model by sequestering miR-96-5p and upregulating RASSF8. Correlation analyses in patient-derived NSCLC tumor specimens supported the involvement of the circPTPRA/miR-96-5p/RASSF8/E-cadherin axis dysregulation in NSCLC tumor progression. INTERPRETATION: circPTPRA suppresses EMT and metastasis of NSCLC cell lines by sponging miR-96-5p, which upregulates the downstream tumor suppressor RASSF8. The circPTPRA/miR-96-5p/RASSF8/E-cadherin axis can be leveraged as a potential treatment avenue in NSCLC. FUND: The Key research and development projects of Anhui Province (201904a0720079), the Natural Science Foundation of Anhui Province (1908085MH240), the Graduate Innovation Program of Bengbu Medical College (Byycx1843), the National Natural Science Foundation of Tibet (XZ2017ZR-ZY033) and the Science and Technology Project of Shannan (SNKJYFJF2017-3) and Academic Subsidy Project for Top Talents in Universities of Anhui in 2019 (gxbjZD16)
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spelling pubmed-66046672019-07-12 The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p Wei, Siliang Zheng, Yuanyuan Jiang, Yanru Li, Xiaojun Geng, Jian Shen, Yuanbing Li, Qin Wang, Xiaojing Zhao, Chengling Chen, Yuqing Qian, Zhongqing Zhou, Jihong Li, Wei EBioMedicine Research paper BACKGROUND: Non-small cell lung carcinomas (NSCLC) are prevalent, lethal cancers with especially grim prospects due to late-stage detection and chemoresistance. Circular RNAs (circRNAs) are non-coding RNAs that participate in tumor development. However, the role of circRNAs in NSCLC is not well known. This study investigated the role of one circRNA – circPTPRA– in NSCLC and characterized its molecular mechanism of action. METHODS: circPTPRA expression was analyzed in human NSCLC tumors and matched healthy lung tissue. We performed functional characterization in NSCLC cell lines and a mouse xenograft model of NSCLC to elucidate the molecular role of circPTPRA in epithelial-mesenchymal transitioning (EMT). We also assessed the regulatory action of circPTPRA on the microRNA miR-96-5p and its target the tumor suppressor Ras association domain-containing protein 8 (RASSF8). FINDINGS: circPTPRA was significantly downregulated in NSCLC tumors relative to matched healthy lung tissue. Lower circPTPRA levels correlated with metastasis and inferior survival outcomes in NSCLC patients. circPTPRA suppressed EMT in NSCLC cell lines and reduced metastasis in the murine xenograft model by sequestering miR-96-5p and upregulating RASSF8. Correlation analyses in patient-derived NSCLC tumor specimens supported the involvement of the circPTPRA/miR-96-5p/RASSF8/E-cadherin axis dysregulation in NSCLC tumor progression. INTERPRETATION: circPTPRA suppresses EMT and metastasis of NSCLC cell lines by sponging miR-96-5p, which upregulates the downstream tumor suppressor RASSF8. The circPTPRA/miR-96-5p/RASSF8/E-cadherin axis can be leveraged as a potential treatment avenue in NSCLC. FUND: The Key research and development projects of Anhui Province (201904a0720079), the Natural Science Foundation of Anhui Province (1908085MH240), the Graduate Innovation Program of Bengbu Medical College (Byycx1843), the National Natural Science Foundation of Tibet (XZ2017ZR-ZY033) and the Science and Technology Project of Shannan (SNKJYFJF2017-3) and Academic Subsidy Project for Top Talents in Universities of Anhui in 2019 (gxbjZD16) Elsevier 2019-05-31 /pmc/articles/PMC6604667/ /pubmed/31160270 http://dx.doi.org/10.1016/j.ebiom.2019.05.032 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Wei, Siliang
Zheng, Yuanyuan
Jiang, Yanru
Li, Xiaojun
Geng, Jian
Shen, Yuanbing
Li, Qin
Wang, Xiaojing
Zhao, Chengling
Chen, Yuqing
Qian, Zhongqing
Zhou, Jihong
Li, Wei
The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p
title The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p
title_full The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p
title_fullStr The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p
title_full_unstemmed The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p
title_short The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p
title_sort circrna circptpra suppresses epithelial-mesenchymal transitioning and metastasis of nsclc cells by sponging mir-96-5p
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604667/
https://www.ncbi.nlm.nih.gov/pubmed/31160270
http://dx.doi.org/10.1016/j.ebiom.2019.05.032
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