The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5pResearch in context
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...
Main Authors: | , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2019-06-01
|
Series: | EBioMedicine |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419303408 |
id |
doaj-30034f086dd04b209f9d73c3ba58de1a |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Siliang Wei Yuanyuan Zheng Yanru Jiang Xiaojun Li Jian Geng Yuanbing Shen Qin Li Xiaojing Wang Chengling Zhao Yuqing Chen Zhongqing Qian Jihong Zhou Wei Li |
spellingShingle |
Siliang Wei Yuanyuan Zheng Yanru Jiang Xiaojun Li Jian Geng Yuanbing Shen Qin Li Xiaojing Wang Chengling Zhao Yuqing Chen Zhongqing Qian Jihong Zhou Wei Li The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5pResearch in context EBioMedicine |
author_facet |
Siliang Wei Yuanyuan Zheng Yanru Jiang Xiaojun Li Jian Geng Yuanbing Shen Qin Li Xiaojing Wang Chengling Zhao Yuqing Chen Zhongqing Qian Jihong Zhou Wei Li |
author_sort |
Siliang Wei |
title |
The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5pResearch in context |
title_short |
The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5pResearch in context |
title_full |
The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5pResearch in context |
title_fullStr |
The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5pResearch in context |
title_full_unstemmed |
The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5pResearch in context |
title_sort |
circrna circptpra suppresses epithelial-mesenchymal transitioning and metastasis of nsclc cells by sponging mir-96-5presearch in context |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2019-06-01 |
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) Keywords: Lung cancer, NSCLC, circRNA, Epithelial-mesenchymal transition, EMT, miR-96-5p |
url |
http://www.sciencedirect.com/science/article/pii/S2352396419303408 |
work_keys_str_mv |
AT siliangwei thecircrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT yuanyuanzheng thecircrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT yanrujiang thecircrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT xiaojunli thecircrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT jiangeng thecircrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT yuanbingshen thecircrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT qinli thecircrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT xiaojingwang thecircrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT chenglingzhao thecircrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT yuqingchen thecircrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT zhongqingqian thecircrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT jihongzhou thecircrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT weili thecircrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT siliangwei circrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT yuanyuanzheng circrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT yanrujiang circrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT xiaojunli circrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT jiangeng circrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT yuanbingshen circrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT qinli circrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT xiaojingwang circrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT chenglingzhao circrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT yuqingchen circrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT zhongqingqian circrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT jihongzhou circrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext AT weili circrnacircptprasuppressesepithelialmesenchymaltransitioningandmetastasisofnsclccellsbyspongingmir965presearchincontext |
_version_ |
1724953839986016256 |
spelling |
doaj-30034f086dd04b209f9d73c3ba58de1a2020-11-25T02:02:18ZengElsevierEBioMedicine2352-39642019-06-0144182193The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5pResearch in contextSiliang Wei0Yuanyuan Zheng1Yanru Jiang2Xiaojun Li3Jian Geng4Yuanbing Shen5Qin Li6Xiaojing Wang7Chengling Zhao8Yuqing Chen9Zhongqing Qian10Jihong Zhou11Wei Li12Department of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, ChinaDepartment of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, ChinaDepartment of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, ChinaDepartment of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu 233004, China; Anhui Province Key Laboratory of Translational Cancer Research, 233004, ChinaDepartment of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, ChinaDepartment of Respiratory Disease, The Second Affiliated Hospital of Bengbu Medical College, Bengbu 233004, ChinaDepartment of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, ChinaDepartment of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, ChinaDepartment of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, ChinaAnhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu, Anhui 233003, ChinaDepartment of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu 233004, China; Anhui Province Key Laboratory of Translational Cancer Research, 233004, China; Correspondence to: J. Zhou, Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu 233004, China.Department of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Provincial Key Laboratory of Respiratory Disease in Anhui, Bengbu 233004, China; Anhui Province Key Laboratory of Translational Cancer Research, 233004, China; Correspondence to: W. Li, Department of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, No. 287 Changhuai Road, Bengbu, Anhui Province, Bengbu 233004, China.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) Keywords: Lung cancer, NSCLC, circRNA, Epithelial-mesenchymal transition, EMT, miR-96-5phttp://www.sciencedirect.com/science/article/pii/S2352396419303408 |