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 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.

A multi‐analyte cell‐free DNA–based blood test for early detection of hepatocellular carcinoma

“…The HelioLiver Test algorithm was developed as outlined in Figure 2 . Interestingly, 10 of the 28 genes in our cfDNA panel are involved in molecular pathways implicated in HCC pathogenesis, [ 24 , 25 ] whereas of the 497 unselected genes, only MLK1 [ 26 ] has been associated in molecular pathways implicated in HCC pathogenesis (Figure S1 ).…”

“…As previously mentioned, we found that several of the 28 genes in our cfDNA panel are involved in molecular pathways implicated in HCC pathogenesis, such as mitogen‐activated protein kinase signaling, interleukin‐17, toll‐like‐receptor‐mediated innate immunity, and T/B‐cell receptor signaling. [ 24 , 25 ] In contrast, only one (MLK1) of the 497 unselected genes [ 26 ] has been associated in molecular pathways implicated in HCC pathogenesis (Figure S1 ). This suggests that our marker selection based solely on their HCC detection performance indeed enriched broad HCC‐pathogenesis‐related pathways, which may not be sufficiently covered by small gene panels.…”

Long non-coding RNA crnde promotes deep vein thrombosis by sequestering miR-181a-5p away from thrombogenic Pcyox1l

“…(5 μm). Hematoxylin (H8070-5 g, Solarbio) was used to stain the sections for 4 min, followed by eosin solution (PT001, Shanghai Bogoo Biological Technology Co., Ltd., Shanghai, China) staining for 2 min [ 21 ]. The morphology was observed under an optical microscope (Olympus BX51, Olympus, Tokyo, Japan).…”

LncRNA H19-rich extracellular vesicles derived from gastric cancer stem cells facilitate tumorigenicity and metastasis via mediating intratumor communication network

“…H&E staining was used for histological observation as previously described [ 19 ]. Tumor and liver tissues of mice were fixed, paraffin-embedded and sectioned (5 μm).…”