LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway
Abstract Background An increasing number of studies have demonstrated that long non-coding RNAs (lncRNAs) play pivotal roles in cancer onset and development. LncRNA AFAP1-AS1 has been validated to be abnormally upregulated and play oncogenic roles in various malignant tumors. The biological role and...
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-019-1363-0 |
| _version_ | 1818195655595655168 |
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| author | Deyao Shi Fashuai Wu Shidai Mu Binwu Hu Binlong Zhong Feng Gao Xiangcheng Qing Jianxiang Liu Zhicai Zhang Zengwu Shao |
| author_facet | Deyao Shi Fashuai Wu Shidai Mu Binwu Hu Binlong Zhong Feng Gao Xiangcheng Qing Jianxiang Liu Zhicai Zhang Zengwu Shao |
| author_sort | Deyao Shi |
| collection | DOAJ |
| description | Abstract Background An increasing number of studies have demonstrated that long non-coding RNAs (lncRNAs) play pivotal roles in cancer onset and development. LncRNA AFAP1-AS1 has been validated to be abnormally upregulated and play oncogenic roles in various malignant tumors. The biological role and mechanism of AFAP1-AS1 in OS (osteosarcoma) remains unclear. Methods Quantitative reverse transcription PCR (qRT-PCR) is applied to examine AFAP1-AS1 expression in OS tissues and OS cell lines. The function of AFAP1-AS1 in OS cells is investigated via in-vitro and in-vivo assays. Western bolt and rescue experiments are applied to detect the expression changes of key molecules including epithelial-mesenchymal transition markers and identify the underlying molecular mechanism. RNA immunoprecipitation is performed to reveal the interaction between AFAP1-AS1 and RhoC. Results AFAP1-AS1 expression is upregulated in human OS tissues and cell lines. AFAP1-AS1 knockdown induces OS cell apoptosis and cell cycle G0/G1 arrest, suppresses OS cells growth, migration, invasion, vasculogenic mimicry formation and epithelial-mesenchymal transition (EMT), and affects actin filament integrity. AFAP1-AS1 knockdown suppresses OS tumor formation and growth in nude mice. AFAP1-AS1 knockdown elicits a signaling inhibition including decreased levels of RhoC, ROCK1, p38MAPK and Twist1. Moreover, AFAP1-AS1 interacts with RhoC. Overexpression of RhoC can partly reverse AFAP1-AS1 downregulation-induced cell EMT inhibition. Conclusions AFAP1-AS1 is overexpressed in osteosarcoma and plays an oncogenic role in osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway, in which RhoC acts as the interaction target of AFAP1-AS1. Our findings indicated a novel molecular mechanism underlying the tumorigenesis and progression of osteosarcoma. AFAP1-AS1 could serve as a promising therapeutic target in OS treatment. |
| first_indexed | 2024-12-12T01:21:38Z |
| format | Article |
| id | doaj.art-efbebe19263a46cd8eeab2b3075ef4ac |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-12T01:21:38Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-efbebe19263a46cd8eeab2b3075ef4ac2022-12-22T00:43:13ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-08-0138111210.1186/s13046-019-1363-0LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathwayDeyao Shi0Fashuai Wu1Shidai Mu2Binwu Hu3Binlong Zhong4Feng Gao5Xiangcheng Qing6Jianxiang Liu7Zhicai Zhang8Zengwu Shao9Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background An increasing number of studies have demonstrated that long non-coding RNAs (lncRNAs) play pivotal roles in cancer onset and development. LncRNA AFAP1-AS1 has been validated to be abnormally upregulated and play oncogenic roles in various malignant tumors. The biological role and mechanism of AFAP1-AS1 in OS (osteosarcoma) remains unclear. Methods Quantitative reverse transcription PCR (qRT-PCR) is applied to examine AFAP1-AS1 expression in OS tissues and OS cell lines. The function of AFAP1-AS1 in OS cells is investigated via in-vitro and in-vivo assays. Western bolt and rescue experiments are applied to detect the expression changes of key molecules including epithelial-mesenchymal transition markers and identify the underlying molecular mechanism. RNA immunoprecipitation is performed to reveal the interaction between AFAP1-AS1 and RhoC. Results AFAP1-AS1 expression is upregulated in human OS tissues and cell lines. AFAP1-AS1 knockdown induces OS cell apoptosis and cell cycle G0/G1 arrest, suppresses OS cells growth, migration, invasion, vasculogenic mimicry formation and epithelial-mesenchymal transition (EMT), and affects actin filament integrity. AFAP1-AS1 knockdown suppresses OS tumor formation and growth in nude mice. AFAP1-AS1 knockdown elicits a signaling inhibition including decreased levels of RhoC, ROCK1, p38MAPK and Twist1. Moreover, AFAP1-AS1 interacts with RhoC. Overexpression of RhoC can partly reverse AFAP1-AS1 downregulation-induced cell EMT inhibition. Conclusions AFAP1-AS1 is overexpressed in osteosarcoma and plays an oncogenic role in osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway, in which RhoC acts as the interaction target of AFAP1-AS1. Our findings indicated a novel molecular mechanism underlying the tumorigenesis and progression of osteosarcoma. AFAP1-AS1 could serve as a promising therapeutic target in OS treatment.http://link.springer.com/article/10.1186/s13046-019-1363-0Long non-coding RNAAFAP1-AS1OsteosarcomaEpithelial-mesenchymal transitionTwist1RhoC |
| spellingShingle | Deyao Shi Fashuai Wu Shidai Mu Binwu Hu Binlong Zhong Feng Gao Xiangcheng Qing Jianxiang Liu Zhicai Zhang Zengwu Shao LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway Journal of Experimental & Clinical Cancer Research Long non-coding RNA AFAP1-AS1 Osteosarcoma Epithelial-mesenchymal transition Twist1 RhoC |
| title | LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway |
| title_full | LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway |
| title_fullStr | LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway |
| title_full_unstemmed | LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway |
| title_short | LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway |
| title_sort | lncrna afap1 as1 promotes tumorigenesis and epithelial mesenchymal transition of osteosarcoma through rhoc rock1 p38mapk twist1 signaling pathway |
| topic | Long non-coding RNA AFAP1-AS1 Osteosarcoma Epithelial-mesenchymal transition Twist1 RhoC |
| url | http://link.springer.com/article/10.1186/s13046-019-1363-0 |
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