Upregulation of RUNX1 Suppresses Proliferation and Migration through Repressing VEGFA Expression in Hepatocellular Carcinoma

Liu, Chao; Xu, Dingwei; Bai, Xue; Li, Jing; Huang, Jie

doi:10.1007/s12253-019-00694-1

Cited by 22 publications

(20 citation statements)

References 28 publications

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“…Paradoxically, RUNX1 has been shown to both directly and indirectly limit the expression of the potent pro-angiogenic factor VEGF. 98 , 174 , 175 This would suggest that RUNX1 may limit angiogenesis in some circumstances, and in support, silencing of RUNX1 in acute myeloid leukaemia cells increased VEGFA promoter activity and conditioned media from these cells led to a significant improvement in the in vitro angiogenic capacity of HUVECs. 175 Like its other functions, it may be that RUNX1 acts in a context-dependent manner and possess the capacity to both stimulate or restrain angiogenic potential depending on the cellular milieu.…”

Section: Runx1 In Non-myocytesmentioning

confidence: 87%

RUNX1: an emerging therapeutic target for cardiovascular disease

Riddell

McBride

Braun

et al. 2020

Cardiovascular Research

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Runt-related transcription factor-1 (RUNX1), also known as acute myeloid leukaemia 1 protein (AML1), is a member of the core-binding factor family of transcription factors which modulate cell proliferation, differentiation, and survival in multiple systems. It is a master-regulator transcription factor, which has been implicated in diverse signalling pathways and cellular mechanisms during normal development and disease. RUNX1 is best characterized for its indispensable role for definitive haematopoiesis and its involvement in haematological malignancies. However, more recently RUNX1 has been identified as a key regulator of adverse cardiac remodelling following myocardial infarction. This review discusses the role RUNX1 plays in the heart and highlights its therapeutic potential as a target to limit the progression of adverse cardiac remodelling and heart failure.

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Section: Runx1 In Non-myocytesmentioning

confidence: 87%

RUNX1: an emerging therapeutic target for cardiovascular disease

Riddell

McBride

Braun

et al. 2020

Cardiovascular Research

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“…On the other hand, Liu et al showed low levels of RUNX1 in HCC. In this respect, these authors believed that hepatic RUNX1 has a tumor suppressor role inhibiting tissue angiogenesis [ 11 ]. Our results provide new evidence on the role of RUNX in NASH in a well-characterized cohort of women with MO.…”

Section: Discussionmentioning

confidence: 99%

“…Runt-related transcription factor 1 (RUNX1), also known as acute myeloid leukemia 1, is a sequence-specific DNA-binding transcription factor that can act as an oncogene or tumor suppressor, depending on its interaction with specific co-regulatory proteins. For example, low levels of RUNX1 have been reported in HCC, indicating its suppressive function [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

The Potential Protective Role of RUNX1 in Nonalcoholic Fatty Liver Disease

Bertran

Pastor

Portillo-Carrasquer

et al. 2021

IJMS

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The pathogenic mechanisms underlying nonalcoholic fatty liver disease (NAFLD) are beginning to be understood. RUNX1 is involved in angiogenesis, which is crucial in inflammation, but its role in nonalcoholic steatohepatitis (NASH) remains unclear. The aim of this study was to analyze RUNX1 mRNA hepatic and jejunal abundance in women with morbid obesity (MO) and NAFLD. RUNX1, lipid metabolism-related genes, and TLRs in women with MO and normal liver (NL, n = 28), NAFLD (n = 41) (simple steatosis (SS, n = 24), or NASH (n = 17)) were analyzed by RT-qPCR. The RUNX1 hepatic expression was higher in SS than in NL or NASH, as likewise confirmed by immunohistochemistry. An increased expression of hepatic FAS was found in NAFLD. Hepatic RUNX1 correlated positively with FAS. There were no significant differences in the jejunum RUNX1 expressions in the different groups. Jejunal FXR expression was lower in NASH than in NL, while the TLR9 expression increased as NAFLD progressed. Jejunal RUNX1 correlated positively with jejunal PPARγ, TLR4, and TLR5. In summary, the hepatic expression of RUNX1 seems to be involved in the first steps of the NAFLD process; however, in NASH, it seems to be downregulated. Our findings provide important insights into the role of RUNX1 in the context of NAFLD/NASH, suggesting a protective role.

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“…With progress in research, researchers found that RUNX1 is associated with tumors of the blood system; besides, it plays a vital part in multiple cancers, such as liver, gastric, breast, non‐small cell lung as well as endometrial cancers . It has been reported that RUNX1 overexpression inhibits the proliferation and migration of liver cancer and promotes the development of lung cancer . Therefore, RUNX1 plays a different role in tumors and can activate or inhibit tumor cell growth and migration among various solid tumors and regulate tumor‐associated gene expression.…”

Section: Introductionmentioning

confidence: 99%

miR‐215‐5p is an anticancer gene in multiple myeloma by targeting RUNX1 and deactivating the PI3K/AKT/mTOR pathway

Liu

Zhang

Huang

et al. 2019

J of Cellular Biochemistry

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This study examined the underlying mechanism of miR‐215‐5p in multiple myeloma (MM) at the molecular level. miR‐215‐5p was upregulated in bone marrow specimens of patients with MM and MM cell lines through real‐time polymerase chain reaction, and downregulation of miR‐215‐5p was related to poor survival of patients with MM. The results of Western blot assay showed that the PI3K/AKT/mTOR signaling pathway was activated in bone marrow specimens of patients with MM. miR‐215‐5p was found to negatively correlate with runt‐related transcription factor 1 (RUNX1) expression in MM clinical bone marrow samples. Therefore, to test the probable mechanisms of the regulation of MM cell proliferation and apoptosis, a miR‐215‐5p mimics/inhibitors/negative control was transfected into MM cells. The targets of miR‐215‐5p were estimated using four bioinformatics databases (including miRDB, miRTarBase, Starbase, and Targetscan). Furthermore, enrichment analyses of gene ontology and Kyoto Encyclopedia of Genomes pathway were carried out at the Enrichr website. Cell viability was detected using the MTT method, while apoptosis and cell cycle were measured using flow cytometry. RUNX1, CDK2, CDC25B, cleaved‐caspase‐3, cleaved‐PARP, p‐PI3K, PI3K, p‐AKT, AKT, p‐mTOR as well as mTOR protein were also investigated using Western blot analysis. According to our findings, miR‐215‐5p overexpression could induce apoptosis while rendering cell cycle arrest at G1 phase and reducing the proliferation of cells. Meanwhile, miRNA‐215‐5p could negatively regulate messengerRNA and protein levels of RUNX1 in MM cells. In addition, there was a similar effect in cell proliferation and apoptosis after miR‐215‐5p mimics or siRNA‐RUNX1 transfection. miR‐215‐5p inhibition inhibited apoptosis while increased the phosphorylation levels of PI3K, AKT, and mTOR proteins, whereas, miR‐215‐5p overexpression increased cell proliferation. Therefore, miR‐215‐5p inhibited MM cell apoptosis via targeting RUNX1 and suppressing the activation of the PI3K/AKT/mTOR pathway.

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Upregulation of RUNX1 Suppresses Proliferation and Migration through Repressing VEGFA Expression in Hepatocellular Carcinoma

Cited by 22 publications

References 28 publications

RUNX1: an emerging therapeutic target for cardiovascular disease

RUNX1: an emerging therapeutic target for cardiovascular disease

The Potential Protective Role of RUNX1 in Nonalcoholic Fatty Liver Disease

miR‐215‐5p is an anticancer gene in multiple myeloma by targeting RUNX1 and deactivating the PI3K/AKT/mTOR pathway

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