Hsa-miR-637 inhibits human hepatocyte proliferation by targeting Med1-interacting proteins
Background: Recent studies have shown that mediator complex subunit 1 (Med1) can significantly affect hepatocyte proliferation and differentiation. Acting as a tumor suppressor, microRNA-637 (hsa-miR-637) can inhibit the growth of hepatocarcinoma cells and further induce cell apoptosis. However, the...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2021-06-01
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| Series: | Liver Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2542568421000027 |
| _version_ | 1818892545974861824 |
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| author | Jing Liu Jianyun Zhu Xiaohong Zhang Yuzhi Jia Xuejun Lee Zhiliang Gao |
| author_facet | Jing Liu Jianyun Zhu Xiaohong Zhang Yuzhi Jia Xuejun Lee Zhiliang Gao |
| author_sort | Jing Liu |
| collection | DOAJ |
| description | Background: Recent studies have shown that mediator complex subunit 1 (Med1) can significantly affect hepatocyte proliferation and differentiation. Acting as a tumor suppressor, microRNA-637 (hsa-miR-637) can inhibit the growth of hepatocarcinoma cells and further induce cell apoptosis. However, the function of hsa-miR-637 and its target genes during liver regeneration remains to be elucidated. Methods: This study used co-immunoprecipitation (Co-IP) assay, transfection, luciferase reporter assay, functional assay by cell counting kit-8 (CCK-8), Annexin V-FITC/propidium iodide apoptosis assay, and quantitative polymerase chain reaction analysis of chromatin immunoprecipitation (ChIP) for analysis. Results: Hsa-miR-637 has been suggested to suppress the expression of two Med1-interacting nuclear receptors, identified as the peroxisome proliferator-activated receptor alpha (PPARA) and thyroid hormone receptor alpha (THRA) at the transcriptional and translational levels in the human liver HL-7702 cell line. The interaction between Med1 and PPARA/THRA in HL-7702 cells was then confirmed. The transcriptional repression of hsa-miR-637 on PPARA and THRA was also demonstrated. Moreover, hsa-miR-637 has been determined to suppress the proliferation of HL-7702 cells. Furthermore, cell cycle arrest of HL-7702 cells was induced by transfection of hsa-miR-637 at the S phase, but its apoptosis failed. Finally, PPARA was indicated to directly bind to the promoter of some transcription factors, like β-catenin, mouse double minute 2 (MDM2), and p53. Conclusions: This study has confirmed that hsa-miR-637 plays an antiproliferative role during liver regeneration, which may contribute in understanding the regenerative process of the liver. |
| first_indexed | 2024-12-19T17:58:25Z |
| format | Article |
| id | doaj.art-63da4afa5024465e9893f5000bdb54f1 |
| institution | Directory Open Access Journal |
| issn | 2542-5684 |
| language | English |
| last_indexed | 2024-12-19T17:58:25Z |
| publishDate | 2021-06-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Liver Research |
| spelling | doaj.art-63da4afa5024465e9893f5000bdb54f12022-12-21T20:11:44ZengKeAi Communications Co., Ltd.Liver Research2542-56842021-06-01528896Hsa-miR-637 inhibits human hepatocyte proliferation by targeting Med1-interacting proteinsJing Liu0Jianyun Zhu1Xiaohong Zhang2Yuzhi Jia3Xuejun Lee4Zhiliang Gao5Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USADepartment of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Corresponding authors. Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Corresponding authors. Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.Background: Recent studies have shown that mediator complex subunit 1 (Med1) can significantly affect hepatocyte proliferation and differentiation. Acting as a tumor suppressor, microRNA-637 (hsa-miR-637) can inhibit the growth of hepatocarcinoma cells and further induce cell apoptosis. However, the function of hsa-miR-637 and its target genes during liver regeneration remains to be elucidated. Methods: This study used co-immunoprecipitation (Co-IP) assay, transfection, luciferase reporter assay, functional assay by cell counting kit-8 (CCK-8), Annexin V-FITC/propidium iodide apoptosis assay, and quantitative polymerase chain reaction analysis of chromatin immunoprecipitation (ChIP) for analysis. Results: Hsa-miR-637 has been suggested to suppress the expression of two Med1-interacting nuclear receptors, identified as the peroxisome proliferator-activated receptor alpha (PPARA) and thyroid hormone receptor alpha (THRA) at the transcriptional and translational levels in the human liver HL-7702 cell line. The interaction between Med1 and PPARA/THRA in HL-7702 cells was then confirmed. The transcriptional repression of hsa-miR-637 on PPARA and THRA was also demonstrated. Moreover, hsa-miR-637 has been determined to suppress the proliferation of HL-7702 cells. Furthermore, cell cycle arrest of HL-7702 cells was induced by transfection of hsa-miR-637 at the S phase, but its apoptosis failed. Finally, PPARA was indicated to directly bind to the promoter of some transcription factors, like β-catenin, mouse double minute 2 (MDM2), and p53. Conclusions: This study has confirmed that hsa-miR-637 plays an antiproliferative role during liver regeneration, which may contribute in understanding the regenerative process of the liver.http://www.sciencedirect.com/science/article/pii/S2542568421000027Liver regenerationHsa-miR-637Peroxisome proliferator-activated receptor alpha (PPARA)Thyroid hormone receptor alpha (THRA)Mediator complex subunit 1(Med1) |
| spellingShingle | Jing Liu Jianyun Zhu Xiaohong Zhang Yuzhi Jia Xuejun Lee Zhiliang Gao Hsa-miR-637 inhibits human hepatocyte proliferation by targeting Med1-interacting proteins Liver Research Liver regeneration Hsa-miR-637 Peroxisome proliferator-activated receptor alpha (PPARA) Thyroid hormone receptor alpha (THRA) Mediator complex subunit 1(Med1) |
| title | Hsa-miR-637 inhibits human hepatocyte proliferation by targeting Med1-interacting proteins |
| title_full | Hsa-miR-637 inhibits human hepatocyte proliferation by targeting Med1-interacting proteins |
| title_fullStr | Hsa-miR-637 inhibits human hepatocyte proliferation by targeting Med1-interacting proteins |
| title_full_unstemmed | Hsa-miR-637 inhibits human hepatocyte proliferation by targeting Med1-interacting proteins |
| title_short | Hsa-miR-637 inhibits human hepatocyte proliferation by targeting Med1-interacting proteins |
| title_sort | hsa mir 637 inhibits human hepatocyte proliferation by targeting med1 interacting proteins |
| topic | Liver regeneration Hsa-miR-637 Peroxisome proliferator-activated receptor alpha (PPARA) Thyroid hormone receptor alpha (THRA) Mediator complex subunit 1(Med1) |
| url | http://www.sciencedirect.com/science/article/pii/S2542568421000027 |
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