Identification and Verification of a Novel MAGI2-AS3/miRNA-374-5p/FOXO1 Network Associated with HBV-Related HCC
Background: Hepatocellular carcinoma (HCC) is a very common neoplasm worldwide, and competitive endogenous RNA (ceRNA) plays an important role in the development of HCC. The purpose of this study is to investigate the molecular mechanisms of ceRNAs in HCC. Methods: This study detects potential ceRNA...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/21/3466 |
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| author | Chao Wang Kunkai Su Hanchao Lin Beini Cen Shusen Zheng Xiao Xu |
| author_facet | Chao Wang Kunkai Su Hanchao Lin Beini Cen Shusen Zheng Xiao Xu |
| author_sort | Chao Wang |
| collection | DOAJ |
| description | Background: Hepatocellular carcinoma (HCC) is a very common neoplasm worldwide, and competitive endogenous RNA (ceRNA) plays an important role in the development of HCC. The purpose of this study is to investigate the molecular mechanisms of ceRNAs in HCC. Methods: This study detects potential ceRNAs from HCC through whole genome analysis of lncRNA, miRNA and mRNA expression. We then performed high-throughput sequencing of tissues from five hepatitis B related HCC patients to screen ceRNAs and those screened ceRNAs expressions were verified on tissues from an independent group of six patients. Finally, the function of ceRNAs of interest was illustrated in vitro. Result: Functional and pathway analysis of The Cancer Genome Atlas revealed ceRNA networks. The high-throughput sequencing identified 985 upregulated and 1612 downregulated lncRNAs and 887 upregulated and 1116 downregulated mRNAs in HCC patients. Differentially expressed genes were parallel to cancer-associated processes, comprising 18 upregulated and 35 downregulated significantly enriched pathways including alcoholism and viral carcinogenesis. Among them, a potential ceRNA network was detected and verified in six HCC patients. CeRNAs of the lncRNA MAGI2-AS3/miR-374-5p/FOXO1 pathway were significantly dysregulated in HCC, and validation in vitro showed that FOXO1 is positively regulated by MAGI2-AS3 through the induction of miR-374a/b-5p in HCC cells. In addition, the overexpression of FOXO1 is associated with proliferation, migration, and invasion of HCC cells and increases apoptosis of HCC cells. MiR-374a/b-5p caused an opposite effect by directly suppressing FOXO1 in HCC cells. Conclusion: CeRNA networks were found in HCC and aberrantly expressed ceRNAs of lncRNA MAGI2-AS3/miR-374-5p/FOXO1 plays a crucial role in HCC, assisting in diagnosis and providing a method for treatment. |
| first_indexed | 2024-03-09T19:11:27Z |
| format | Article |
| id | doaj.art-8d1f2c21935b40a2b5aabe573c5f4894 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T19:11:27Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-8d1f2c21935b40a2b5aabe573c5f48942023-11-24T04:09:17ZengMDPI AGCells2073-44092022-11-011121346610.3390/cells11213466Identification and Verification of a Novel MAGI2-AS3/miRNA-374-5p/FOXO1 Network Associated with HBV-Related HCCChao Wang0Kunkai Su1Hanchao Lin2Beini Cen3Shusen Zheng4Xiao Xu5Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, ChinaKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaNHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou 310003, ChinaKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaBackground: Hepatocellular carcinoma (HCC) is a very common neoplasm worldwide, and competitive endogenous RNA (ceRNA) plays an important role in the development of HCC. The purpose of this study is to investigate the molecular mechanisms of ceRNAs in HCC. Methods: This study detects potential ceRNAs from HCC through whole genome analysis of lncRNA, miRNA and mRNA expression. We then performed high-throughput sequencing of tissues from five hepatitis B related HCC patients to screen ceRNAs and those screened ceRNAs expressions were verified on tissues from an independent group of six patients. Finally, the function of ceRNAs of interest was illustrated in vitro. Result: Functional and pathway analysis of The Cancer Genome Atlas revealed ceRNA networks. The high-throughput sequencing identified 985 upregulated and 1612 downregulated lncRNAs and 887 upregulated and 1116 downregulated mRNAs in HCC patients. Differentially expressed genes were parallel to cancer-associated processes, comprising 18 upregulated and 35 downregulated significantly enriched pathways including alcoholism and viral carcinogenesis. Among them, a potential ceRNA network was detected and verified in six HCC patients. CeRNAs of the lncRNA MAGI2-AS3/miR-374-5p/FOXO1 pathway were significantly dysregulated in HCC, and validation in vitro showed that FOXO1 is positively regulated by MAGI2-AS3 through the induction of miR-374a/b-5p in HCC cells. In addition, the overexpression of FOXO1 is associated with proliferation, migration, and invasion of HCC cells and increases apoptosis of HCC cells. MiR-374a/b-5p caused an opposite effect by directly suppressing FOXO1 in HCC cells. Conclusion: CeRNA networks were found in HCC and aberrantly expressed ceRNAs of lncRNA MAGI2-AS3/miR-374-5p/FOXO1 plays a crucial role in HCC, assisting in diagnosis and providing a method for treatment.https://www.mdpi.com/2073-4409/11/21/3466hepatocellular carcinomabioinformatics analysisceRNAslncRNA MAGI2-AS3/miR-374-5p/FOXO1 network |
| spellingShingle | Chao Wang Kunkai Su Hanchao Lin Beini Cen Shusen Zheng Xiao Xu Identification and Verification of a Novel MAGI2-AS3/miRNA-374-5p/FOXO1 Network Associated with HBV-Related HCC Cells hepatocellular carcinoma bioinformatics analysis ceRNAs lncRNA MAGI2-AS3/miR-374-5p/FOXO1 network |
| title | Identification and Verification of a Novel MAGI2-AS3/miRNA-374-5p/FOXO1 Network Associated with HBV-Related HCC |
| title_full | Identification and Verification of a Novel MAGI2-AS3/miRNA-374-5p/FOXO1 Network Associated with HBV-Related HCC |
| title_fullStr | Identification and Verification of a Novel MAGI2-AS3/miRNA-374-5p/FOXO1 Network Associated with HBV-Related HCC |
| title_full_unstemmed | Identification and Verification of a Novel MAGI2-AS3/miRNA-374-5p/FOXO1 Network Associated with HBV-Related HCC |
| title_short | Identification and Verification of a Novel MAGI2-AS3/miRNA-374-5p/FOXO1 Network Associated with HBV-Related HCC |
| title_sort | identification and verification of a novel magi2 as3 mirna 374 5p foxo1 network associated with hbv related hcc |
| topic | hepatocellular carcinoma bioinformatics analysis ceRNAs lncRNA MAGI2-AS3/miR-374-5p/FOXO1 network |
| url | https://www.mdpi.com/2073-4409/11/21/3466 |
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