MKL1 regulates hepatocellular carcinoma cell proliferation, migration and apoptosis via the COMPASS complex and NF-κB signaling

Abstract Background Histone modification plays essential roles in hepatocellular carcinoma (HCC) pathogenesis, but the regulatory mechanisms remain poorly understood. In this study, we aimed to analyze the roles of Megakaryoblastic leukemia 1 (MKL1) and its regulation of COMPASS (complex of proteins...

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Autores principales:	Zhao Liu, Jiuzheng Sun, Chuanzhi Li, Liyou Xu, Jun Liu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Ash2 Hepatocellular carcinoma MKL1 p65 Wdr5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e067cbbac2b04c19834bbb59caa76973
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spelling	oai:doaj.org-article:e067cbbac2b04c19834bbb59caa769732021-11-08T11:02:15ZMKL1 regulates hepatocellular carcinoma cell proliferation, migration and apoptosis via the COMPASS complex and NF-κB signaling10.1186/s12885-021-08185-w1471-2407https://doaj.org/article/e067cbbac2b04c19834bbb59caa769732021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08185-whttps://doaj.org/toc/1471-2407Abstract Background Histone modification plays essential roles in hepatocellular carcinoma (HCC) pathogenesis, but the regulatory mechanisms remain poorly understood. In this study, we aimed to analyze the roles of Megakaryoblastic leukemia 1 (MKL1) and its regulation of COMPASS (complex of proteins associated with Set1) in HCC cells. Methods MKL1 expression in clinical tissues and cell lines were detected by bioinformatics, qRT-PCR and western blot. MKL1 expression in HCC cells were silenced with siRNA, followed by cell proliferation evaluation via Edu staining and colony formation, migration and invasion using the Transwell system, and apoptosis by Hoechst staining. HCC cell tumorigenesis was assessed by cancer cell line-based xenograft model, combined with H&E staining and IHC assays. Results MKL1 expression was elevated in HCC cells and clinical tissues which was correlated with poor prognosis. MKL1 silencing significantly repressed proliferation, migration, invasion and colony formation but enhanced apoptosis in HepG2 and Huh-7 cells. MKL1 silencing also inhibited COMPASS components and p65 protein expression in HepG2 and Huh-7 cells. HepG2 cell tumorigenesis in nude mice was severely impaired by MKL1 knockdown, resulted into suppressed Ki67 expression and cell proliferation. Conclusion MKL1 promotes HCC pathogenesis by regulating hepatic cell proliferation, migration and apoptosis via the COMPASS complex and NF-κB signaling.Zhao LiuJiuzheng SunChuanzhi LiLiyou XuJun LiuBMCarticleAsh2Hepatocellular carcinomaMKL1p65Wdr5Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ash2 Hepatocellular carcinoma MKL1 p65 Wdr5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Ash2 Hepatocellular carcinoma MKL1 p65 Wdr5 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Zhao Liu Jiuzheng Sun Chuanzhi Li Liyou Xu Jun Liu MKL1 regulates hepatocellular carcinoma cell proliferation, migration and apoptosis via the COMPASS complex and NF-κB signaling
description	Abstract Background Histone modification plays essential roles in hepatocellular carcinoma (HCC) pathogenesis, but the regulatory mechanisms remain poorly understood. In this study, we aimed to analyze the roles of Megakaryoblastic leukemia 1 (MKL1) and its regulation of COMPASS (complex of proteins associated with Set1) in HCC cells. Methods MKL1 expression in clinical tissues and cell lines were detected by bioinformatics, qRT-PCR and western blot. MKL1 expression in HCC cells were silenced with siRNA, followed by cell proliferation evaluation via Edu staining and colony formation, migration and invasion using the Transwell system, and apoptosis by Hoechst staining. HCC cell tumorigenesis was assessed by cancer cell line-based xenograft model, combined with H&E staining and IHC assays. Results MKL1 expression was elevated in HCC cells and clinical tissues which was correlated with poor prognosis. MKL1 silencing significantly repressed proliferation, migration, invasion and colony formation but enhanced apoptosis in HepG2 and Huh-7 cells. MKL1 silencing also inhibited COMPASS components and p65 protein expression in HepG2 and Huh-7 cells. HepG2 cell tumorigenesis in nude mice was severely impaired by MKL1 knockdown, resulted into suppressed Ki67 expression and cell proliferation. Conclusion MKL1 promotes HCC pathogenesis by regulating hepatic cell proliferation, migration and apoptosis via the COMPASS complex and NF-κB signaling.
format	article
author	Zhao Liu Jiuzheng Sun Chuanzhi Li Liyou Xu Jun Liu
author_facet	Zhao Liu Jiuzheng Sun Chuanzhi Li Liyou Xu Jun Liu
author_sort	Zhao Liu
title	MKL1 regulates hepatocellular carcinoma cell proliferation, migration and apoptosis via the COMPASS complex and NF-κB signaling
title_short	MKL1 regulates hepatocellular carcinoma cell proliferation, migration and apoptosis via the COMPASS complex and NF-κB signaling
title_full	MKL1 regulates hepatocellular carcinoma cell proliferation, migration and apoptosis via the COMPASS complex and NF-κB signaling
title_fullStr	MKL1 regulates hepatocellular carcinoma cell proliferation, migration and apoptosis via the COMPASS complex and NF-κB signaling
title_full_unstemmed	MKL1 regulates hepatocellular carcinoma cell proliferation, migration and apoptosis via the COMPASS complex and NF-κB signaling
title_sort	mkl1 regulates hepatocellular carcinoma cell proliferation, migration and apoptosis via the compass complex and nf-κb signaling
publisher	BMC
publishDate	2021
url	https://doaj.org/article/e067cbbac2b04c19834bbb59caa76973
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MKL1 regulates hepatocellular carcinoma cell proliferation, migration and apoptosis via the COMPASS complex and NF-κB signaling

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