Piezo1 promoted hepatocellular carcinoma progression and EMT through activating TGF-β signaling by recruiting Rab5c
Abstract Background Piezo1 has been revealed to play a regulatory role in vascular development and progression of variety tumors. However, whether and how the progression of hepatocellular carcinoma (HCC) regulated by Piezo1 remains elusive. This study aimed to elucidate the effect and mechanisms of...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-022-02574-2 |
| _version_ | 1818523468718669824 |
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| author | Yi-ming Li Cong Xu Bo Sun Fang-jing Zhong Momo Cao Lian-yue Yang |
| author_facet | Yi-ming Li Cong Xu Bo Sun Fang-jing Zhong Momo Cao Lian-yue Yang |
| author_sort | Yi-ming Li |
| collection | DOAJ |
| description | Abstract Background Piezo1 has been revealed to play a regulatory role in vascular development and progression of variety tumors. However, whether and how the progression of hepatocellular carcinoma (HCC) regulated by Piezo1 remains elusive. This study aimed to elucidate the effect and mechanisms of Piezo1 in HCC. Methods The mRNA and protein expression level of Piezo1 in HCC samples and cell lines was determined by qRT-PCR, western blot and immunohistochemistry analyses. Two independent study cohorts containing 280 patients were analyzed to reveal the association between Piezo1 expression and clinicopathological characteristics. Series of in vitro and in vivo experiments were used to validate the function of Piezo1 in HCC. Gene set enrichment analysis (GSEA) was performed to explore the signaling pathway of Piezo1. Immunoprecipitation, immunofluorescence and in vitro and in vivo experiments were used to explore the molecular mechanism of Piezo1 in HCC progression. Results Our results demonstrated the Piezo1 expression was significantly upregulated in HCC tissues and cell lines, and upregulation of Piezo1 closely correlated with aggressive clinicopathological features and poor prognosis. Knockdown of Piezo1 in HCCLM3 and Hep3B cells significantly restrained proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) of HCC cells in vitro, and tumor growth, metastasis, EMT in vivo. TGF-β signaling pathway was most significant enriched pathway in GSEA. Finally, tumor promotion effect of Piezo1 was found to exerted through recruiting and combining Rab5c to activating TGF-β signaling pathway. Conclusions Piezo1 significantly related to poor prognosis and promotes progression of hepatocellular carcinoma via activating TGF-β signaling, which suggesting that Piezo1 may serve as a novel prognostic predictor and the potential therapeutic target for HCC patients. |
| first_indexed | 2024-12-11T05:45:17Z |
| format | Article |
| id | doaj.art-c7a38c7c841e434ea9e60eac2a5bd60a |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-11T05:45:17Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-c7a38c7c841e434ea9e60eac2a5bd60a2022-12-22T01:18:59ZengBMCCancer Cell International1475-28672022-04-0122111910.1186/s12935-022-02574-2Piezo1 promoted hepatocellular carcinoma progression and EMT through activating TGF-β signaling by recruiting Rab5cYi-ming Li0Cong Xu1Bo Sun2Fang-jing Zhong3Momo Cao4Lian-yue Yang5Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South UniversityLiver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South UniversityLiver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South UniversityLiver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South UniversityLiver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South UniversityLiver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South UniversityAbstract Background Piezo1 has been revealed to play a regulatory role in vascular development and progression of variety tumors. However, whether and how the progression of hepatocellular carcinoma (HCC) regulated by Piezo1 remains elusive. This study aimed to elucidate the effect and mechanisms of Piezo1 in HCC. Methods The mRNA and protein expression level of Piezo1 in HCC samples and cell lines was determined by qRT-PCR, western blot and immunohistochemistry analyses. Two independent study cohorts containing 280 patients were analyzed to reveal the association between Piezo1 expression and clinicopathological characteristics. Series of in vitro and in vivo experiments were used to validate the function of Piezo1 in HCC. Gene set enrichment analysis (GSEA) was performed to explore the signaling pathway of Piezo1. Immunoprecipitation, immunofluorescence and in vitro and in vivo experiments were used to explore the molecular mechanism of Piezo1 in HCC progression. Results Our results demonstrated the Piezo1 expression was significantly upregulated in HCC tissues and cell lines, and upregulation of Piezo1 closely correlated with aggressive clinicopathological features and poor prognosis. Knockdown of Piezo1 in HCCLM3 and Hep3B cells significantly restrained proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) of HCC cells in vitro, and tumor growth, metastasis, EMT in vivo. TGF-β signaling pathway was most significant enriched pathway in GSEA. Finally, tumor promotion effect of Piezo1 was found to exerted through recruiting and combining Rab5c to activating TGF-β signaling pathway. Conclusions Piezo1 significantly related to poor prognosis and promotes progression of hepatocellular carcinoma via activating TGF-β signaling, which suggesting that Piezo1 may serve as a novel prognostic predictor and the potential therapeutic target for HCC patients.https://doi.org/10.1186/s12935-022-02574-2Piezo1Hepatocellular carcinomaPrognosisCancer progressionTGF-β signalingEMT |
| spellingShingle | Yi-ming Li Cong Xu Bo Sun Fang-jing Zhong Momo Cao Lian-yue Yang Piezo1 promoted hepatocellular carcinoma progression and EMT through activating TGF-β signaling by recruiting Rab5c Cancer Cell International Piezo1 Hepatocellular carcinoma Prognosis Cancer progression TGF-β signaling EMT |
| title | Piezo1 promoted hepatocellular carcinoma progression and EMT through activating TGF-β signaling by recruiting Rab5c |
| title_full | Piezo1 promoted hepatocellular carcinoma progression and EMT through activating TGF-β signaling by recruiting Rab5c |
| title_fullStr | Piezo1 promoted hepatocellular carcinoma progression and EMT through activating TGF-β signaling by recruiting Rab5c |
| title_full_unstemmed | Piezo1 promoted hepatocellular carcinoma progression and EMT through activating TGF-β signaling by recruiting Rab5c |
| title_short | Piezo1 promoted hepatocellular carcinoma progression and EMT through activating TGF-β signaling by recruiting Rab5c |
| title_sort | piezo1 promoted hepatocellular carcinoma progression and emt through activating tgf β signaling by recruiting rab5c |
| topic | Piezo1 Hepatocellular carcinoma Prognosis Cancer progression TGF-β signaling EMT |
| url | https://doi.org/10.1186/s12935-022-02574-2 |
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