ArticleOncogene2014
LXRα-mediated downregulation of FOXM1 suppresses the proliferation of hepatocellular carcinoma cells.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
- The oncogenic role of FOXM1 in hepatocellular carcinoma: molecular mechanisms, clinical significance, and therapeutic potentials.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Biomarkers in COPD-Associated PH/CCP: Circulating Molecules and Cell-Intrinsic Marker.International journal of chronic obstructive pulmonary disease · 2025Review
- Psilostachyin C reduces malignant properties of hepatocellular carcinoma cells by blocking CREBBP-mediated transcription of GATAD2B.Functional & integrative genomics · 2024Article
- Review
- Liver X Receptors (LXRs) in cancer-an Eagle's view on molecular insights and therapeutic opportunities.Frontiers in cell and developmental biology · 2024Review
- Dysregulated cholesterol regulatory genes in hepatocellular carcinoma.European journal of medical research · 2023Review
- Emerging Insights into Liver X Receptor α in the Tumorigenesis and Therapeutics of Human Cancers.Biomolecules · 2023Review
- RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer.JCI insight · 2023Article
- FOXM1: Functional Roles of FOXM1 in Non-Malignant Diseases.Biomolecules · 2023Review
- SR9009 inhibits lethal prostate cancer subtype 1 by regulating the LXRα/FOXM1 pathway independently of REV-ERBs.Cell death & disease · 2022Article
- A lignan from Alnus japonica inhibits glioblastoma tumorspheres by suppression of FOXM1.Scientific reports · 2022Article
- The human FOXM1 homolog promotes basal progenitor cell proliferation and cortical folding in mouse.EMBO reports · 2022Article
- PPARγ attenuates hepatic inflammation and oxidative stress of non‑alcoholic steatohepatitis via modulating the miR‑21‑5p/SFRP5 pathway.Molecular medicine reports · 2021Article
- RNA-Seq Reveals Different Gene Expression in Liver-Specific Prohibitin 1 Knock-Out Mice.Frontiers in physiology · 2021Article
- Reciprocal Regulation Between Forkhead Box M1/NF-κB and Methionine Adenosyltransferase 1A Drives Liver Cancer.Hepatology (Baltimore, Md.) · 2020Article
- Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas.Journal of cellular and molecular medicine · 2020Article
- EGFR/FOXO3A/LXR-α Axis Promotes Prostate Cancer Proliferation and Metastasis and Dual-Targeting LXR-α/EGFR Shows Synthetic Lethality.Frontiers in oncology · 2020Article
- Withaferin A Acts as a Novel Regulator of Liver X Receptor-α in HCC.Frontiers in oncology · 2020Article
- Liver X Receptor Agonism Sensitizes a Subset of Hepatocellular Carcinoma to Sorafenib by Dual-Inhibiting MET and EGFR.Neoplasia (New York, N.Y.) · 2020Article
- FOXM1 functions collaboratively with PLAU to promote gastric cancer progression.Journal of Cancer · 2020Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver X receptors (LXRs), including LXRα and LXRβ isoforms, have important roles in the metabolic regulation of glucose, cholesterol and lipid. Moreover, activation of LXRs also represses the expression of cyclin D1 and cyclin B1, and thus suppresses the proliferation of multiple cancer cells, but the relevant mechanism is not well known. Forkhead box M1 (FOXM1) is a proliferation-specific member of forkhead box family, which is highly expressed in proliferating normal cells and numerous cancer cells. FOXM1 directly activates transcription of cyclin D1 and cyclin B1, resulting in the enhancement of cell cycle progression and cell proliferation. However, it is unclear whether LXRs are involved in the regulation of FOXM1. In this study, we demonstrated that specific LXRs agonists downregulated expression of FOXM1, cyclin D1 and cyclin B1 in hepatocellular carcinoma (HCC) cells, which led to cell cycle and cell proliferation arrest. Knockdown of FOXM1 significantly alleviated LXRs activation-mediated cell cycle arrest and cell growth suppression. Reporter assays showed that the activation of LXRs significantly reduced the transcriptional activity of FOXM1 promoter. Electrophoretic mobility shift assay and chromatin immunoprecipitation assays demonstrated that LXRα but not LXRβ could bind to an inverted repeat IR2 (-52CCGTCAcgTGACCT-39) in the promoter region of FOXM1 gene. Moreover, the xenograft tumor growth and the corresponding FOXM1 expression in nude mice were dramatically repressed by LXRs agonists. Taken together, we conclude that LXRα but not LXRβ functions as a transcriptional repressor for FOXM1 expression. The pathway 'LXRα-FOXM1-cyclin D1/cyclin B1' is a novel mechanism by which LXRs suppress the proliferation of HCC cells, suggesting that the pathway may be a novel target for HCC treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.