MKL1 通过 COMPASS 复合物和 NF-κB 信号通路调控肝癌细胞的增殖、迁移和凋亡。
MKL1 regulates hepatocellular carcinoma cell proliferation, migration and apoptosis via the COMPASS complex and NF-κB signaling.
机构信息
Department of Hepatobiliary and Pancreatic Surgery, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
出版信息
BMC Cancer. 2021 Nov 6;21(1):1184. doi: 10.1186/s12885-021-08185-w.
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.
背景
组蛋白修饰在肝细胞癌（HCC）发病机制中发挥着重要作用，但调控机制仍知之甚少。在这项研究中，我们旨在分析巨核细胞白血病 1（MKL1）及其对 COMPASS（与 Set1 相关的蛋白复合物）在 HCC 细胞中的调控作用。
方法
通过生物信息学、qRT-PCR 和 Western blot 检测 MKL1 在临床组织和细胞系中的表达。用 siRNA 沉默 HCC 细胞中的 MKL1 表达，然后通过 Edu 染色评估细胞增殖，用 Transwell 系统评估迁移和侵袭，用 Hoechst 染色评估凋亡。通过基于癌细胞系的异种移植模型结合 H&E 染色和 IHC 检测评估 HCC 细胞的肿瘤发生。
结果
MKL1 在 HCC 细胞和临床组织中表达上调，与预后不良相关。MKL1 沉默显著抑制 HepG2 和 Huh-7 细胞的增殖、迁移、侵袭和集落形成，但促进凋亡。MKL1 沉默还抑制了 HepG2 和 Huh-7 细胞中 COMPASS 成分和 p65 蛋白的表达。MKL1 敲低严重抑制了 HepG2 细胞在裸鼠中的致瘤性，导致 Ki67 表达和细胞增殖受到抑制。
结论
MKL1 通过调节 COMPASS 复合物和 NF-κB 信号通路促进 HCC 的发生发展，从而调节肝母细胞的增殖、迁移和凋亡。
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