Knockdown of FoxM1 by siRNA interference decreases cell proliferation, induces cell cycle arrest and inhibits cell invasion in MHCC-97H cells in vitro

Wu, Qifei; Liu, Chang; Tai, Ming-Hui; Liu, Dong; Lei, Lei; Wang, Ruitao; Tian, Mingyi; Lü, Yi

doi:10.1038/aps.2010.4

Cited by 57 publications

(36 citation statements)

References 20 publications

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“…Furthermore, either FOXM1 allele deficiency or inhibition of FoXM1 function diminished tumor growth and proliferation in mouse liver tumors (7). In addition, knockdown of FoXM1 by sirnA inhibited proliferation and invasion of human Hcc cells in vitro (8). these data strongly suggest that FoXM1 plays a crucial role in hepatocarcinogenesis and tumor progression, which may support the notion that FoXM1 expression could be associated with malignant potential and unfavorable prognosis of Hcc.…”

Section: Introductionsupporting

confidence: 68%

“…the evolutionarily conserved forkhead box (Fox) family genes of transcriptional regulators consist of more than 50 mammalian proteins that share homology in the winged helix DnA-binding domain (6)(7)(8)(9)(10)(11). of the Fox members, Forkhead box M1 (FoXM1) protein shows some uniqueness, being abundantly expressed in the transformed cells and a variety of human cancers but undetectable in various differentiated cells and quiescent adult tissues (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

“…of the Fox members, Forkhead box M1 (FoXM1) protein shows some uniqueness, being abundantly expressed in the transformed cells and a variety of human cancers but undetectable in various differentiated cells and quiescent adult tissues (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). It has recently been shown that conditional deletion of FoXM1 expression in mouse hepatocytes resulted in failure in cell proliferation and resistance to liver tumor induction by diethylnitrosamine (Den)/phenobarbital (PB) (6).…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of Forkhead box M1 protein associates with aggressive tumor features and poor prognosis of hepatocellular carcinoma

Sun

Li²,

Lu³

et al. 2011

Oncol Rep

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Abstract. the aim of this study was to detect the expression of the Forkhead box M1 (FoXM1) protein in human hepatocellular carcinoma (Hcc) and to associate FoXM1 expression with clinicopathological features of the patients, and predict the prognosis of patients with FoXM1 expression. surgical tissue specimens from 151 Hcc patients were subjected to a tissue microarray construction and immunohistochemistry analysis of FoXM1 and the proliferation marker proliferating cell nuclear antigen (pcnA). the data showed that the FoXM1 protein was expressed in 59.3% of the Hcc tissues, which was significantly higher compared to that of the surrounding non-tumorous tissues (23.8%; p<0.001). Moreover, FoXM1 expression was positively correlated with the labeling index of pcnA (p<0.001) in Hcc and with aggressive tumor phenotypes, such as larger tumor size, multiple tumors, bilobar involvement, poor tumor cell differentiation, advanced stage and macrovascular invasion (p<0.05). In addition, Hcc patients with FoXM1-positive tumors had a poorer recurrencefree and overall survival after hepatectomy than those with FoXM1-negative tumors. Multivariate cox regression analysis demonstrated that FoXM1 expression was an independent predictor of unfavorable outcome (p<0.05). the data from the current study suggest that FoXM1 may play an important role in Hcc progression and could be further evaluated as a prognostic biomarker and potential therapeutic target.

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Section: Introductionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Overexpression of Forkhead box M1 protein associates with aggressive tumor features and poor prognosis of hepatocellular carcinoma

Sun

Li²,

Lu³

et al. 2011

Oncol Rep

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show abstract

“…The downregulation of FOXM1 by siRNA in vitro decreases DNA replication as well as angiogenic and metastatic potential (Wang and Gartel, 2011;Wu et al, 2010;Halasi and Gartel, 2012;. A number of proteasome inhibitors have been shown to decrease FOXM1 levels, probably by stabilizing an unidentified negative regulator of FOXM1 (Gartel, 2010), and many of these inhibitors are currently used in cancer treatments; most of their effects are likely to be due, at least in part, to FOXM1 downregulation.…”

Section: Box 1 Anti-foxm1 Agents As Potential Cancer Therapiesmentioning

confidence: 99%

Fox transcription factors: from development to disease

2016

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Forkhead box (Fox) transcription factors are evolutionarily conserved in organisms ranging from yeast to humans. They regulate diverse biological processes both during development and throughout adult life. Mutations in many Fox genes are associated with human disease and, as such, various animal models have been generated to study the function of these transcription factors in mechanistic detail. In many cases, the absence of even a single Fox transcription factor is lethal. In this Primer, we provide an overview of the Fox family, highlighting several key Fox transcription factor families that are important for mammalian development.

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“…The expression of FOXM1 is frequently upregulated in many solid tumors (7). The overexpression of FOXM1 promotes proliferation, invasion and epithelial-mesenchymal transition, and is associated with a poor prognosis in HCC (8)(9)(10). Recent studies also revealed that FOXM1 promotes glucose consumption, lactate production and increased lactate dehydrogenase A (LDHA) activity in different cells, suggesting a pivotal role , MENG PU 1* , YU LI 2 and DESHENG WANG for FOXM1 in the regulation of cell aerobic glycolysis (11,12).…”

Section: Introductionmentioning

confidence: 99%

FOXM1 regulates glycolysis in hepatocellular carcinoma by transactivating glucose transporter 1 expression

Shang

Liu

et al. 2017

Oncology Reports

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Abstract. The Forkhead box M1 (FOXM1) transcription factor plays crucial roles in the initiation and progression of various malignancies, including hepatocellular carcinoma (HCC). However, the mechanism by which FOXM1 regulates cancer metabolism remains unclear. In the present study, overexpression and RNA interference (RNAi) approaches were used to investigate the role of FOXM1 in the regulation of glycolysis in vitro. Luciferase reporter assays were used to explore the transcriptional regulation of the glucose transporter 1 (GLUT1) promoter by FOXM1. Then, immunohistochemical staining was used to examine the expression of FOXM1 and GLUT1 in 100 paired HCC and adjacent non-cancerous liver tissues. Chi-square test and logistic regression analysis were performed to evaluate the association between FOXM1 and GLUT1 expression with clinicopathological characteristics. Our data showed that FOXM1 promoted glycolysis in the HCC cells. FOXM1 knockdown significantly reduced the expression of GLUT1 among key glycolysis-related molecules in the different HCC cell lines. Glucose uptake and lactate production assay showed that FOXM1 positively regulated glycolysis based on GLUT1 expression. Moreover, FOXM1 overexpression increased and knockdown decreased GLUT1 expression. Luciferase reporter assays showed that the -206 to -199 bp region of the GLUT1 promoter is important for FOXM1 to enhance GLUT1 promoter activity. The results of the IHC analysis showed that the protein expression of FOXM1 and GLUT1 was closely related to the tumor histological grade and TNM stage. In addition, GLUT1 expression was also related to microvascular invasion. In conclusion, overexpression of FOXM1 and GLUT1 may play critical roles in HCC. FOXM1 promotes HCC glycolysis by transactivating GLUT1 expression. IntroductionHepatocellular carcinoma (HCC) is one of the most prevalent neoplasms and the second leading cause of cancer-related mortality worldwide (1). Despite the application of surgical resection, ablation, embolization and other therapeutic methods, the overall prognosis of patients with HCC remains poor and the incidence of HCC is increasing annually (2,3). Therefore, the underlying mechanisms that promote the pathogenesis of this deadly disease must be further investigated.Metabolic reprogramming has long been linked to cancer. One of the classical theories of metabolic abnormality in tumors is the Warburg effect, which describes increased glycolysis even under normal oxygen conditions (4). The shift of the metabolic pathway from oxidative phosphorylation to glycolysis is more rapid to meet the demands necessary for the process of tumor progression. However, it is inefficient to generate ATP by consuming units of glucose under glycolysis conditions (5). Therefore, transformed cells need to uptake more glucose than normal cells. The glucose transporter 1 (GLUT1) isoform is a key rate-limiting protein in the transport of glucose and is overexpressed in HCC (6). However, the mechanism underlying increased glycolysis by targeting GLUT1 in HCC...

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Knockdown of FoxM1 by siRNA interference decreases cell proliferation, induces cell cycle arrest and inhibits cell invasion in MHCC-97H cells in vitro

Cited by 57 publications

References 20 publications

Overexpression of Forkhead box M1 protein associates with aggressive tumor features and poor prognosis of hepatocellular carcinoma

Overexpression of Forkhead box M1 protein associates with aggressive tumor features and poor prognosis of hepatocellular carcinoma

Fox transcription factors: from development to disease

FOXM1 regulates glycolysis in hepatocellular carcinoma by transactivating glucose transporter 1 expression

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