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The forkhead box M1 (FOXM1) expression and antitumor effect of FOXM1 inhibition in malignant rhabdoid tumor
- Source :
- Journal of cancer research and clinical oncology. 147(5)
- Publication Year :
- 2020
-
Abstract
- Malignant rhabdoid tumor (MRT) is a rare, highly aggressive sarcoma with an uncertain cell of origin. Despite the existing standard of intensive multimodal therapy, the prognosis of patients with MRT is very poor. Novel antitumor agents are needed for MRT patients. Forkhead box transcription factor 1 (FOXM1) is overexpressed and is correlated with the pathogenesis in several human malignancies. In this study, we identified the clinicopathological and prognostic values of the expression of FOXM1 and its roles in the progression of MRT. We investigated the FOXM1 expression levels and their clinical significance in 23 MRT specimens using immunohistochemistry and performed clinicopathologic and prognostic analyses. We also demonstrated correlations between the downregulation of FOXM1 and oncological characteristics using small interfering RNA (siRNA) and FOXM1 inhibitor in MRT cell lines. Histopathological analyses revealed that primary renal MRTs showed significantly low FOXM1 protein expression levels (p = 0.032); however, there were no significant differences in other clinicopathological characteristics or the survival rate. FOXM1 siRNA and FOXM1 inhibitor (thiostrepton) successfully downregulated the mRNA and protein expression of FOXM1 in vitro and the downregulation of FOXM1 inhibited cell proliferation, drug resistance to chemotherapeutic agents, migration, invasion, and caused the cell cycle arrest and apoptosis of MRT cell lines. A cDNA microarray analysis showed that FOXM1 regulated FANCD2 and NBS1, which are key genes for DNA damage repair. This study demonstrates that FOXM1 may serve as a promising therapeutic target for MRT.
- Subjects :
- 0301 basic medicine
Male
Cancer Research
Small interfering RNA
Down-Regulation
Antineoplastic Agents
Apoptosis
Biology
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Cell Movement
Cell Line, Tumor
medicine
Humans
RNA, Messenger
RNA, Small Interfering
Rhabdoid Tumor
Cell Proliferation
Microarray analysis techniques
Cell growth
Fanconi Anemia Complementation Group D2 Protein
Forkhead Box Protein M1
Infant
Nuclear Proteins
General Medicine
Cell Cycle Checkpoints
Cell cycle
medicine.disease
Prognosis
Immunohistochemistry
Thiostrepton
Gene Expression Regulation, Neoplastic
Survival Rate
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
FOXM1
Cancer research
Female
Sarcoma
DNA Damage
Subjects
Details
- ISSN :
- 14321335
- Volume :
- 147
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of cancer research and clinical oncology
- Accession number :
- edsair.doi.dedup.....6e0dacf22afc5850da0d056779d838f9