Long non-coding RNA PVT1 regulates the migration of hepatocellular carcinoma HepG2 cells via miR-3619-5p/MKL1 axis
Hepatocellular carcinoma (HCC) is the third most common malignant tumor of the digestive system. Plasma cell tumor heterotopic gene 1 (PVT1) is an intergenic long non-coding RNA that is aberrantly expressed in different cancers. Myocardin-related transcription factor A or megakaryoblastic leukemia...
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| Format: | Article |
| Language: | English |
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Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2021-04-01
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| Series: | Biomolecules & Biomedicine |
| Subjects: | |
| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/4641 |
| _version_ | 1797261295784820736 |
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| author | Hua Liu Yan Yin Ting Liu Yanying Gao Qing Ye Junqing Yan Fushuang Ha |
| author_facet | Hua Liu Yan Yin Ting Liu Yanying Gao Qing Ye Junqing Yan Fushuang Ha |
| author_sort | Hua Liu |
| collection | DOAJ |
| description |
Hepatocellular carcinoma (HCC) is the third most common malignant tumor of the digestive system. Plasma cell tumor heterotopic gene 1 (PVT1) is an intergenic long non-coding RNA that is aberrantly expressed in different cancers. Myocardin-related transcription factor A or megakaryoblastic leukemia 1 (MKL1) is a transcriptional coactivator of serum response factor that has been shown to promote cancer cell migration and invasion. In this study, we investigated the relationship between PVT1 and MKL1 as a novel regulatory mechanism underlying HCC progression. We used HepG2 and Cos‑7 cell lines. Transfection experiments with miR-3619-5p mimics/inhibitor, PVT1, siRNA-PVT1, MKL1, or siRNA-MKL1 were performed. RNA and protein levels were analyzed by quantitative reverse transcription PCR and Western blot, respectively. Cell migration was assessed by transwell assay. Luciferase assays, RNA-FISH, RNA immunoprecipitation, and chromatin immunoprecipitation assays were performed to confirm the interaction between PVT1, miR-3619-5p, and MKL1 in HCC cells. Overexpression of PVT1 was positively correlated with MKL1 upregulation, which promoted HepG2 cell migration. miR-3619-5p inhibited MKL1 expression in HCC cells by acting on its 3′-UTR. Furthermore, PVT1 promoted MKL1 expression and migration in HCC cells by directly binding to miR-3619-5p. In a positive feedback loop, MKL1 could activate PVT1 transcription by binding to the CArG box in the promoter region. Our findings may provide a basis for the development of novel targeted therapies in HCC.
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| first_indexed | 2024-04-24T23:38:57Z |
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| id | doaj.art-5d48e1b74a794b6da47be5202fba0c19 |
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| issn | 2831-0896 2831-090X |
| language | English |
| last_indexed | 2024-04-24T23:38:57Z |
| publishDate | 2021-04-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
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| series | Biomolecules & Biomedicine |
| spelling | doaj.art-5d48e1b74a794b6da47be5202fba0c192024-03-15T13:44:23ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2021-04-0121210.17305/bjbms.2020.4641Long non-coding RNA PVT1 regulates the migration of hepatocellular carcinoma HepG2 cells via miR-3619-5p/MKL1 axisHua Liu0https://orcid.org/0000-0002-0035-9086Yan Yin1Ting Liu2https://orcid.org/0000-0002-4173-8963Yanying Gao3https://orcid.org/0000-0002-8893-9295Qing Ye4https://orcid.org/0000-0001-5205-237XJunqing Yan5https://orcid.org/0000-0002-8715-5341 Fushuang Ha6https://orcid.org/0000-0001-6951-2432The Third Central Hospital of Tianjin, Tianjin, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Artificial Cell Engineering Technology Research Center, Tianjin, China; Tianjin Institute of Hepatobiliary Disease, Tianjin, ChinaRespiratory and Critical Care Medicine of Tianjin Chest Hospital, Tianjin, ChinaTianjin Institute of Cardiovascular Disease, Tianjin Chest Hospital, Tianjin, ChinaThe Third Central Hospital of Tianjin, Tianjin, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Artificial Cell Engineering Technology Research Center, Tianjin, China; Tianjin Institute of Hepatobiliary Disease, Tianjin, ChinaThe Third Central Hospital of Tianjin, Tianjin, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Artificial Cell Engineering Technology Research Center, Tianjin, China; Tianjin Institute of Hepatobiliary Disease, Tianjin, ChinaThe Third Central Hospital of Tianjin, Tianjin, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Artificial Cell Engineering Technology Research Center, Tianjin, China; Tianjin Institute of Hepatobiliary Disease, Tianjin, ChinaThe Third Central Hospital of Tianjin, Tianjin, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China; Artificial Cell Engineering Technology Research Center, Tianjin, China; Tianjin Institute of Hepatobiliary Disease, Tianjin, China Hepatocellular carcinoma (HCC) is the third most common malignant tumor of the digestive system. Plasma cell tumor heterotopic gene 1 (PVT1) is an intergenic long non-coding RNA that is aberrantly expressed in different cancers. Myocardin-related transcription factor A or megakaryoblastic leukemia 1 (MKL1) is a transcriptional coactivator of serum response factor that has been shown to promote cancer cell migration and invasion. In this study, we investigated the relationship between PVT1 and MKL1 as a novel regulatory mechanism underlying HCC progression. We used HepG2 and Cos‑7 cell lines. Transfection experiments with miR-3619-5p mimics/inhibitor, PVT1, siRNA-PVT1, MKL1, or siRNA-MKL1 were performed. RNA and protein levels were analyzed by quantitative reverse transcription PCR and Western blot, respectively. Cell migration was assessed by transwell assay. Luciferase assays, RNA-FISH, RNA immunoprecipitation, and chromatin immunoprecipitation assays were performed to confirm the interaction between PVT1, miR-3619-5p, and MKL1 in HCC cells. Overexpression of PVT1 was positively correlated with MKL1 upregulation, which promoted HepG2 cell migration. miR-3619-5p inhibited MKL1 expression in HCC cells by acting on its 3′-UTR. Furthermore, PVT1 promoted MKL1 expression and migration in HCC cells by directly binding to miR-3619-5p. In a positive feedback loop, MKL1 could activate PVT1 transcription by binding to the CArG box in the promoter region. Our findings may provide a basis for the development of novel targeted therapies in HCC. https://www.bjbms.org/ojs/index.php/bjbms/article/view/4641PVT1miR-3619-5pMKL1cell migrationhepatocellular carcinomaHCC |
| spellingShingle | Hua Liu Yan Yin Ting Liu Yanying Gao Qing Ye Junqing Yan Fushuang Ha Long non-coding RNA PVT1 regulates the migration of hepatocellular carcinoma HepG2 cells via miR-3619-5p/MKL1 axis Biomolecules & Biomedicine PVT1 miR-3619-5p MKL1 cell migration hepatocellular carcinoma HCC |
| title | Long non-coding RNA PVT1 regulates the migration of hepatocellular carcinoma HepG2 cells via miR-3619-5p/MKL1 axis |
| title_full | Long non-coding RNA PVT1 regulates the migration of hepatocellular carcinoma HepG2 cells via miR-3619-5p/MKL1 axis |
| title_fullStr | Long non-coding RNA PVT1 regulates the migration of hepatocellular carcinoma HepG2 cells via miR-3619-5p/MKL1 axis |
| title_full_unstemmed | Long non-coding RNA PVT1 regulates the migration of hepatocellular carcinoma HepG2 cells via miR-3619-5p/MKL1 axis |
| title_short | Long non-coding RNA PVT1 regulates the migration of hepatocellular carcinoma HepG2 cells via miR-3619-5p/MKL1 axis |
| title_sort | long non coding rna pvt1 regulates the migration of hepatocellular carcinoma hepg2 cells via mir 3619 5p mkl1 axis |
| topic | PVT1 miR-3619-5p MKL1 cell migration hepatocellular carcinoma HCC |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/4641 |
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