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...
Main Authors: | , , , , , , |
---|---|
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 |
_version_ | 1798042513835032576 |
---|---|
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. |
first_indexed | 2024-04-11T22:36:31Z |
format | Article |
id | doaj.art-3ef9ce263a9449bbb830908de46f92c4 |
institution | Directory Open Access Journal |
issn | 1479-5876 |
language | English |
last_indexed | 2024-04-11T22:36:31Z |
publishDate | 2022-08-01 |
publisher | BMC |
record_format | Article |
series | Journal of Translational Medicine |
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 |
work_keys_str_mv | AT qingchen lncrnagas6as1facilitatestumorigenesisandmetastasisofcolorectalcancerbyregulatingtrim14throughmir3703pmir12965pandfus AT linzhou lncrnagas6as1facilitatestumorigenesisandmetastasisofcolorectalcancerbyregulatingtrim14throughmir3703pmir12965pandfus AT dema lncrnagas6as1facilitatestumorigenesisandmetastasisofcolorectalcancerbyregulatingtrim14throughmir3703pmir12965pandfus AT juanhou lncrnagas6as1facilitatestumorigenesisandmetastasisofcolorectalcancerbyregulatingtrim14throughmir3703pmir12965pandfus AT yuxinlin lncrnagas6as1facilitatestumorigenesisandmetastasisofcolorectalcancerbyregulatingtrim14throughmir3703pmir12965pandfus AT jiewu lncrnagas6as1facilitatestumorigenesisandmetastasisofcolorectalcancerbyregulatingtrim14throughmir3703pmir12965pandfus AT mintao lncrnagas6as1facilitatestumorigenesisandmetastasisofcolorectalcancerbyregulatingtrim14throughmir3703pmir12965pandfus |