LncRNA PVT1 activated by TGF-β1/Smad3 facilitates proliferation and metastasis of hepatocellular carcinoma via upregulating Smad6 and NRG1
Abstract Background Hepatocellular carcinoma (HCC) significantly affects the patient’s physical and mental health. Long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) has been associated with the progression of HCC. However, the current effectiveness of HCC treatment is considered...
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BMC
2025-05-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06229-4 |
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| author | Shuaihui Wu Qian Cheng Yang Shi Kunlei Wang Zhinan Chen Xinyin Li Ping Jiang Zhixiang Cheng Zhiyong Yang Bo Liao |
| author_facet | Shuaihui Wu Qian Cheng Yang Shi Kunlei Wang Zhinan Chen Xinyin Li Ping Jiang Zhixiang Cheng Zhiyong Yang Bo Liao |
| author_sort | Shuaihui Wu |
| collection | DOAJ |
| description | Abstract Background Hepatocellular carcinoma (HCC) significantly affects the patient’s physical and mental health. Long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) has been associated with the progression of HCC. However, the current effectiveness of HCC treatment is considered insufficient, and the scope of its therapeutic targets is highly limited. The purpose of this investigation is to investigate the pathogenic mechanism of PVT1 in HCC and assess its potential for gene therapy in HCC. Methods This study assessed cycle phases and proliferative capacity of HCC cells through flow cytometry, CCK-8 assay, EdU, and colony formation assays. Chromatin Immunoprecipitation (ChIP) and Dual-Luciferase Reporter Assays were conducted to investigate the interactions among the promoter and PVT1, PVT1 and its target miRNAs, as well as miRNAs and their target genes. BALB/c nude mice were employed to establish models for studying the proliferation and metastasis of HCC in vivo. Results The data revealed that TGF-β1 upregulates PVT1, while Smad3 functions as a transcription factor to modulate PVT1. PVT1, in turn, upregulates Smad6 and NRG1 (Neuregulin 1). Moreover, PVT1 combines with miR-186-5p and miR-143-3p, while miR-186-5p inhibits Smad6 and miR-143-3p inhibits NRG1. Further, in vivo and in vitro analyses revealed that PVT1 stimulates the expression of Smad6, thereby promoting the proliferation of HCC. In addition, PVT1 also promotes the spread of HCC by upregulating NRG1. Conclusion This study validated that PVT1 activated by TGF-β1/Smad3 facilitates HCC progression and metastasis by upregulating the miR-186-5p/Smad6 and miR-143-3p/NRG1 axes, indicating its potential as a biological target for treating HCC. |
| format | Article |
| id | doaj-art-6ce09166bd0d4860843b31d6fa9bc1d7 |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-6ce09166bd0d4860843b31d6fa9bc1d72025-08-20T02:10:53ZengBMCJournal of Translational Medicine1479-58762025-05-0123111710.1186/s12967-025-06229-4LncRNA PVT1 activated by TGF-β1/Smad3 facilitates proliferation and metastasis of hepatocellular carcinoma via upregulating Smad6 and NRG1Shuaihui Wu0Qian Cheng1Yang Shi2Kunlei Wang3Zhinan Chen4Xinyin Li5Ping Jiang6Zhixiang Cheng7Zhiyong Yang8Bo Liao9Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityAbstract Background Hepatocellular carcinoma (HCC) significantly affects the patient’s physical and mental health. Long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) has been associated with the progression of HCC. However, the current effectiveness of HCC treatment is considered insufficient, and the scope of its therapeutic targets is highly limited. The purpose of this investigation is to investigate the pathogenic mechanism of PVT1 in HCC and assess its potential for gene therapy in HCC. Methods This study assessed cycle phases and proliferative capacity of HCC cells through flow cytometry, CCK-8 assay, EdU, and colony formation assays. Chromatin Immunoprecipitation (ChIP) and Dual-Luciferase Reporter Assays were conducted to investigate the interactions among the promoter and PVT1, PVT1 and its target miRNAs, as well as miRNAs and their target genes. BALB/c nude mice were employed to establish models for studying the proliferation and metastasis of HCC in vivo. Results The data revealed that TGF-β1 upregulates PVT1, while Smad3 functions as a transcription factor to modulate PVT1. PVT1, in turn, upregulates Smad6 and NRG1 (Neuregulin 1). Moreover, PVT1 combines with miR-186-5p and miR-143-3p, while miR-186-5p inhibits Smad6 and miR-143-3p inhibits NRG1. Further, in vivo and in vitro analyses revealed that PVT1 stimulates the expression of Smad6, thereby promoting the proliferation of HCC. In addition, PVT1 also promotes the spread of HCC by upregulating NRG1. Conclusion This study validated that PVT1 activated by TGF-β1/Smad3 facilitates HCC progression and metastasis by upregulating the miR-186-5p/Smad6 and miR-143-3p/NRG1 axes, indicating its potential as a biological target for treating HCC.https://doi.org/10.1186/s12967-025-06229-4Hepatocellular carcinomalncRNA PVT1TGF-β1Smad3Smad6P21 |
| spellingShingle | Shuaihui Wu Qian Cheng Yang Shi Kunlei Wang Zhinan Chen Xinyin Li Ping Jiang Zhixiang Cheng Zhiyong Yang Bo Liao LncRNA PVT1 activated by TGF-β1/Smad3 facilitates proliferation and metastasis of hepatocellular carcinoma via upregulating Smad6 and NRG1 Journal of Translational Medicine Hepatocellular carcinoma lncRNA PVT1 TGF-β1 Smad3 Smad6 P21 |
| title | LncRNA PVT1 activated by TGF-β1/Smad3 facilitates proliferation and metastasis of hepatocellular carcinoma via upregulating Smad6 and NRG1 |
| title_full | LncRNA PVT1 activated by TGF-β1/Smad3 facilitates proliferation and metastasis of hepatocellular carcinoma via upregulating Smad6 and NRG1 |
| title_fullStr | LncRNA PVT1 activated by TGF-β1/Smad3 facilitates proliferation and metastasis of hepatocellular carcinoma via upregulating Smad6 and NRG1 |
| title_full_unstemmed | LncRNA PVT1 activated by TGF-β1/Smad3 facilitates proliferation and metastasis of hepatocellular carcinoma via upregulating Smad6 and NRG1 |
| title_short | LncRNA PVT1 activated by TGF-β1/Smad3 facilitates proliferation and metastasis of hepatocellular carcinoma via upregulating Smad6 and NRG1 |
| title_sort | lncrna pvt1 activated by tgf β1 smad3 facilitates proliferation and metastasis of hepatocellular carcinoma via upregulating smad6 and nrg1 |
| topic | Hepatocellular carcinoma lncRNA PVT1 TGF-β1 Smad3 Smad6 P21 |
| url | https://doi.org/10.1186/s12967-025-06229-4 |
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