Epigenetically regulated mi R-145 suppresses colon cancer invasion and metastasis by targeting LASP1
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摘要
Background and Aim:Mi R-145 is a tumor-suppressive micro RNA that participates in the malignant progression of colorectal cancer(CRC).Although mi R-145 has been reported to inhibit proliferation and to induce apoptosis of CRC cells,the reports about its role in invasion and metastasis are controversial.The regulation of mi R-145 its own expression also requires further elucidation.To further explore these unsettled problems,we carried out this study.Methods:We overexpressed exogenous mi R-145 and inhibited endogenous mi R-145 in CRC cell lines to investigate the roles of this micro RNA in invasion and metastasis both in vitro and in vivo.We confirmed the target of mi R-145 through direct binding assays and verifications on CRC patients' tissue specimens.We validated the co-regulation of histone methylation and transcription factors on mi R-145 expression by luciferase report and chromatin immunoprecipitation(Ch IP) assays in the promoter region of mi R-145.Results:In this study,we firstly found that mi R-145 is markedly downregulated in the metastatic tumors of CRC patients and that mi R-145 suppresses the invasion and metastasis of CRC cells.We also proved that LIM and SH3 protein 1(LASP1) is a direct target of mi R-145.Furthermore,we identified the core promoter regions of mi R-145 and observed the cooperation between histone methylation and transcription factors through binding to these core promoter regions to regulate the expression of mi R-145 in CRC cells.Conclusion:We found that mi R-145,regulated by the cooperation between histone methylation and transcription factors through binding to its core promoter regions,suppresses the invasion and metastasis of CRC by directly targeting LASP1,thus providing an insight into the regulatory network in CRC cells and offering new targets for treating CRC patients.
Background and Aim:Mi R-145 is a tumor-suppressive micro RNA that participates in the malignant progression of colorectal cancer(CRC).Although mi R-145 has been reported to inhibit proliferation and to induce apoptosis of CRC cells,the reports about its role in invasion and metastasis are controversial.The regulation of mi R-145 its own expression also requires further elucidation.To further explore these unsettled problems,we carried out this study.Methods:We overexpressed exogenous mi R-145 and inhibited endogenous mi R-145 in CRC cell lines to investigate the roles of this micro RNA in invasion and metastasis both in vitro and in vivo.We confirmed the target of mi R-145 through direct binding assays and verifications on CRC patients' tissue specimens.We validated the co-regulation of histone methylation and transcription factors on mi R-145 expression by luciferase report and chromatin immunoprecipitation(Ch IP) assays in the promoter region of mi R-145.Results:In this study,we firstly found that mi R-145 is markedly downregulated in the metastatic tumors of CRC patients and that mi R-145 suppresses the invasion and metastasis of CRC cells.We also proved that LIM and SH3 protein 1(LASP1) is a direct target of mi R-145.Furthermore,we identified the core promoter regions of mi R-145 and observed the cooperation between histone methylation and transcription factors through binding to these core promoter regions to regulate the expression of mi R-145 in CRC cells.Conclusion:We found that mi R-145,regulated by the cooperation between histone methylation and transcription factors through binding to its core promoter regions,suppresses the invasion and metastasis of CRC by directly targeting LASP1,thus providing an insight into the regulatory network in CRC cells and offering new targets for treating CRC patients.
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