LncRNA GAS6-AS1 facilitates tumorigenesis and metastasis of colorectal cancer by regulating TRIM14 through miR-370-3p/miR-1296-5p and FUS

Abstract Background Long non-coding RNAs (lncRNAs) are essential regulators of tumorigenesis and the development of colorectal cancer (CRC). Here, we aimed to investigate the role of lncRNA GAS6-AS1 in CRC and its potential mechanisms. Methods Bioinformatics analyses evaluated the level of GAS6-AS1...

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Main Authors: Qing Chen, Lin Zhou, De Ma, Juan Hou, Yuxin Lin, Jie Wu, Min Tao
Format: Article
Language:English
Published: BMC 2022-08-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-022-03550-0
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author Qing Chen
Lin Zhou
De Ma
Juan Hou
Yuxin Lin
Jie Wu
Min Tao
author_facet Qing Chen
Lin Zhou
De Ma
Juan Hou
Yuxin Lin
Jie Wu
Min Tao
author_sort Qing Chen
collection DOAJ
description Abstract Background Long non-coding RNAs (lncRNAs) are essential regulators of tumorigenesis and the development of colorectal cancer (CRC). Here, we aimed to investigate the role of lncRNA GAS6-AS1 in CRC and its potential mechanisms. Methods Bioinformatics analyses evaluated the level of GAS6-AS1 in colon cancer, its correlation with clinicopathological factors, survival curve and diagnostic value. qRT-PCR were performed to detect the GAS6-AS1 level in CRC samples and cell lines. The CCK8, EdU, scratch healing, transwell assays and animal experiments were conducted to investigate the function of GAS6-AS1 in CRC. RNA immunoprecipitation (RIP) and dual-luciferase reporter gene analyses were carried out to reveal interaction between GAS6-AS1, TRIM14, FUS, and miR-370-3p/miR-1296-5p. Results GAS6-AS1 was greatly elevated in CRC and positively associated with unfavorable prognosis of CRC patients. Functionally, GAS6-AS1 positively regulates CRC proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and induces CRC growth and metastasis in vivo. Moreover, GAS6-AS1 exerted oncogenic function by competitively binding to miR-370-3p and miR-1296-5p, thereby upregulating TRIM14. Furthermore, we verified that GAS6-AS1 and TRIM14 both interact with FUS and that GAS6-AS1 stabilized TRIM14 mRNA by recruiting FUS. Besides, rescue experiments furtherly demonstrated that GAS6-AS1 facilitate progression of CRC by regulating TRIM14. Conclusion Collectively, these findings demonstrate that GAS6-AS1 promotes TRIM14-mediated cell proliferation, migration, invasion, and EMT of CRC via ceRNA network and FUS-dependent manner, suggesting that GAS6-AS1 could be utilized as a novel biomarker and therapeutic target for CRC.
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spelling doaj.art-3ef9ce263a9449bbb830908de46f92c42022-12-22T03:59:11ZengBMCJournal of Translational Medicine1479-58762022-08-0120111510.1186/s12967-022-03550-0LncRNA GAS6-AS1 facilitates tumorigenesis and metastasis of colorectal cancer by regulating TRIM14 through miR-370-3p/miR-1296-5p and FUSQing Chen0Lin Zhou1De Ma2Juan Hou3Yuxin Lin4Jie Wu5Min Tao6Department of Oncology, Jingjiang People’s Hospital, The Seventh Affiliated Hospital of Yangzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Soochow UniversityDepartment of Oncology, Jingjiang People’s Hospital, The Seventh Affiliated Hospital of Yangzhou UniversityDepartment of Oncology, Jingjiang People’s Hospital, The Seventh Affiliated Hospital of Yangzhou UniversityDepartment of Urology, The First Affiliated Hospital of Soochow UniversityDepartment of Oncology, The First Affiliated Hospital of Soochow UniversityDepartment of Oncology, The First Affiliated Hospital of Soochow UniversityAbstract Background Long non-coding RNAs (lncRNAs) are essential regulators of tumorigenesis and the development of colorectal cancer (CRC). Here, we aimed to investigate the role of lncRNA GAS6-AS1 in CRC and its potential mechanisms. Methods Bioinformatics analyses evaluated the level of GAS6-AS1 in colon cancer, its correlation with clinicopathological factors, survival curve and diagnostic value. qRT-PCR were performed to detect the GAS6-AS1 level in CRC samples and cell lines. The CCK8, EdU, scratch healing, transwell assays and animal experiments were conducted to investigate the function of GAS6-AS1 in CRC. RNA immunoprecipitation (RIP) and dual-luciferase reporter gene analyses were carried out to reveal interaction between GAS6-AS1, TRIM14, FUS, and miR-370-3p/miR-1296-5p. Results GAS6-AS1 was greatly elevated in CRC and positively associated with unfavorable prognosis of CRC patients. Functionally, GAS6-AS1 positively regulates CRC proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and induces CRC growth and metastasis in vivo. Moreover, GAS6-AS1 exerted oncogenic function by competitively binding to miR-370-3p and miR-1296-5p, thereby upregulating TRIM14. Furthermore, we verified that GAS6-AS1 and TRIM14 both interact with FUS and that GAS6-AS1 stabilized TRIM14 mRNA by recruiting FUS. Besides, rescue experiments furtherly demonstrated that GAS6-AS1 facilitate progression of CRC by regulating TRIM14. Conclusion Collectively, these findings demonstrate that GAS6-AS1 promotes TRIM14-mediated cell proliferation, migration, invasion, and EMT of CRC via ceRNA network and FUS-dependent manner, suggesting that GAS6-AS1 could be utilized as a novel biomarker and therapeutic target for CRC.https://doi.org/10.1186/s12967-022-03550-0Long non-coding RNAsGAS6-AS1TRIM14FUSmiR-370-3pmiR-1296-5p
spellingShingle Qing Chen
Lin Zhou
De Ma
Juan Hou
Yuxin Lin
Jie Wu
Min Tao
LncRNA GAS6-AS1 facilitates tumorigenesis and metastasis of colorectal cancer by regulating TRIM14 through miR-370-3p/miR-1296-5p and FUS
Journal of Translational Medicine
Long non-coding RNAs
GAS6-AS1
TRIM14
FUS
miR-370-3p
miR-1296-5p
title LncRNA GAS6-AS1 facilitates tumorigenesis and metastasis of colorectal cancer by regulating TRIM14 through miR-370-3p/miR-1296-5p and FUS
title_full LncRNA GAS6-AS1 facilitates tumorigenesis and metastasis of colorectal cancer by regulating TRIM14 through miR-370-3p/miR-1296-5p and FUS
title_fullStr LncRNA GAS6-AS1 facilitates tumorigenesis and metastasis of colorectal cancer by regulating TRIM14 through miR-370-3p/miR-1296-5p and FUS
title_full_unstemmed LncRNA GAS6-AS1 facilitates tumorigenesis and metastasis of colorectal cancer by regulating TRIM14 through miR-370-3p/miR-1296-5p and FUS
title_short LncRNA GAS6-AS1 facilitates tumorigenesis and metastasis of colorectal cancer by regulating TRIM14 through miR-370-3p/miR-1296-5p and FUS
title_sort lncrna gas6 as1 facilitates tumorigenesis and metastasis of colorectal cancer by regulating trim14 through mir 370 3p mir 1296 5p and fus
topic Long non-coding RNAs
GAS6-AS1
TRIM14
FUS
miR-370-3p
miR-1296-5p
url https://doi.org/10.1186/s12967-022-03550-0
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