Paclitaxel-induced inhibition of NSCLC invasion and migration via RBFOX3-mediated circIGF1R biogenesis
Abstract We previously reported that circIGF1R is significantly downregulated in non-small cell lung cancer (NSCLC) cells and tissues. It inhibits cancer cell invasion and migration, although the underlying molecular mechanisms remain elusive. The invasion and migration of NSCLC cells was analyzed b...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-51500-1 |
| _version_ | 1797355792382296064 |
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| author | Zhanyu Xu Liping Zheng Shikang Li |
| author_facet | Zhanyu Xu Liping Zheng Shikang Li |
| author_sort | Zhanyu Xu |
| collection | DOAJ |
| description | Abstract We previously reported that circIGF1R is significantly downregulated in non-small cell lung cancer (NSCLC) cells and tissues. It inhibits cancer cell invasion and migration, although the underlying molecular mechanisms remain elusive. The invasion and migration of NSCLC cells was analyzed by routine in vivo and in vitro functional assays. Fluorescent in situ hybridization, luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation (RIP) assay were performed to explore the molecular mechanisms. Mechanism of action of paclitaxel-induced RBFOX3-mediated inhibition of NSCLC invasion and migration was investigated through in vitro and in vivo experiments.Our study reveals that circIGF1R acts as a Competing Endogenous RNA (ceRNA) for miR-1270, thereby regulating Van-Gogh-like 2 (VANGL2) expression and subsequently inhibiting NSCLC cell invasion and migration via the Wnt pathway. We also found that RNA binding protein fox-1 homolog 3 (RBFOX3) enhances circIGF1R biogenesis by binding to IGF1R pre-mRNA, which in turn suppresses migration and invasion in NSCLC cells. Additionally, the chemotherapeutic drug paclitaxel was shown to impede NSCLC invasion and migration by inducing RBFOX3-mediated circIGF1R biogenesis.RBFOX3 inhibits the invasion and migration of NSCLC cells through the circIGF1R/ miR-1270/VANGL2 axis, circIGF1R has the potential to serve as a biomarker and therapeutic target for NSCLC. |
| first_indexed | 2024-03-08T14:16:12Z |
| format | Article |
| id | doaj.art-7f101ec1f4d449d3a1134600c8321d3d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T14:16:12Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7f101ec1f4d449d3a1134600c8321d3d2024-01-14T12:21:34ZengNature PortfolioScientific Reports2045-23222024-01-0114111410.1038/s41598-024-51500-1Paclitaxel-induced inhibition of NSCLC invasion and migration via RBFOX3-mediated circIGF1R biogenesisZhanyu Xu0Liping Zheng1Shikang Li2Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Anesthesia Catheter Room, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical UniversityAbstract We previously reported that circIGF1R is significantly downregulated in non-small cell lung cancer (NSCLC) cells and tissues. It inhibits cancer cell invasion and migration, although the underlying molecular mechanisms remain elusive. The invasion and migration of NSCLC cells was analyzed by routine in vivo and in vitro functional assays. Fluorescent in situ hybridization, luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation (RIP) assay were performed to explore the molecular mechanisms. Mechanism of action of paclitaxel-induced RBFOX3-mediated inhibition of NSCLC invasion and migration was investigated through in vitro and in vivo experiments.Our study reveals that circIGF1R acts as a Competing Endogenous RNA (ceRNA) for miR-1270, thereby regulating Van-Gogh-like 2 (VANGL2) expression and subsequently inhibiting NSCLC cell invasion and migration via the Wnt pathway. We also found that RNA binding protein fox-1 homolog 3 (RBFOX3) enhances circIGF1R biogenesis by binding to IGF1R pre-mRNA, which in turn suppresses migration and invasion in NSCLC cells. Additionally, the chemotherapeutic drug paclitaxel was shown to impede NSCLC invasion and migration by inducing RBFOX3-mediated circIGF1R biogenesis.RBFOX3 inhibits the invasion and migration of NSCLC cells through the circIGF1R/ miR-1270/VANGL2 axis, circIGF1R has the potential to serve as a biomarker and therapeutic target for NSCLC.https://doi.org/10.1038/s41598-024-51500-1 |
| spellingShingle | Zhanyu Xu Liping Zheng Shikang Li Paclitaxel-induced inhibition of NSCLC invasion and migration via RBFOX3-mediated circIGF1R biogenesis Scientific Reports |
| title | Paclitaxel-induced inhibition of NSCLC invasion and migration via RBFOX3-mediated circIGF1R biogenesis |
| title_full | Paclitaxel-induced inhibition of NSCLC invasion and migration via RBFOX3-mediated circIGF1R biogenesis |
| title_fullStr | Paclitaxel-induced inhibition of NSCLC invasion and migration via RBFOX3-mediated circIGF1R biogenesis |
| title_full_unstemmed | Paclitaxel-induced inhibition of NSCLC invasion and migration via RBFOX3-mediated circIGF1R biogenesis |
| title_short | Paclitaxel-induced inhibition of NSCLC invasion and migration via RBFOX3-mediated circIGF1R biogenesis |
| title_sort | paclitaxel induced inhibition of nsclc invasion and migration via rbfox3 mediated circigf1r biogenesis |
| url | https://doi.org/10.1038/s41598-024-51500-1 |
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