Regulation of the master regulator FOXM1 in cancer

Liao, Guobin; Li, Xin‐Zhe; Zeng, Shuo; Liu, Cheng; Yang, Shiming; Li, Yang; Hu, C.; Bai, Jianying

doi:10.1186/s12964-018-0266-6

Cited by 301 publications

(299 citation statements)

References 137 publications

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“…Our previous report supported the opposite finding, ie, that BrdU-LIs did not increase in the residual kidneys of adult male rats after UNx (Matsushita et al, 2015). This inconsis- including kidney tumor cells (Kalin, Ustiyan, & Kalinichenko, 2011;Liang et al, 2018;Liao et al, 2018;Zhao et al, 2018). FOXM1 plays critical roles in cell division of these cells, and FOXM1-mediated cell F I G U R E 1 Cell proliferative activities in the residual kidneys of rats after unilateral nephrectomy (UNx).…”

Section: Discussionsupporting

confidence: 66%

“…Canonical pathways related to the cell cycle were activated by UNx in both male and female rats cycle progression is involved in the G 1 /S and G 2 /M transitions (Halasi & Gartel, 2013;Kalin et al, 2011;Saldivar et al, 2018). (Liao et al, 2018). Therefore, we performed comprehensive analysis of miRNA expression, followed by mRNA/miRNA integrated analysis to investigate the detailed mechanisms of FOXM1 regulation in compensation in the kidney.…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive expression analysis of mRNA and microRNA for the investigation of compensatory mechanisms in the rat kidney after unilateral nephrectomy

Matsushita

Toyoda

Yamada

et al. 2020

J of Applied Toxicology

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Compensation is a physiological response that occurs during chemical exposure to maintain homeostasis. Because compensatory responses are not usually considered adverse effects, it is important to understand compensatory mechanisms for chemical risk assessment. Although the kidney is a major target organ for toxicity, there is controversy over whether hyperplasia or hypertrophy contributes to the compensatory mechanism, and there is limited information to apply for chemical risk assessment. In the present study, compensatory mechanisms of the kidney were investigated in a unilateral nephrectomy (UNx) model using adult male and female F344 rats. In residual kidneys of male and female rats after UNx, 5‐bromo‐2′‐deoxyuridine‐labeling indices and mRNA expression of cell cycle‐related genes were increased, although there were no fluctuations in mRNA expression of transforming growth factor‐β1, which contributes to hypertrophy in renal tubules. Pathway analysis using mRNA expression data from a complementary DNA (cDNA) microarray revealed that canonical pathways related to cell proliferation were mainly activated and that forkhead box M1 (FOXM1) was an upstream regulator of compensatory cell proliferation in residual kidneys of male and female rats. cDNA microarray for microRNAs (miRNAs) demonstrated that nine miRNAs were downregulated in residual kidneys, and mRNA/miRNA integrated analysis indicated that miRNAs were associated with the expression of factors downstream of FOXM1. Overall, these results suggested that FOXM1‐mediated hyperplasia rather than hypertrophy contributed to compensatory mechanisms in the kidney and that miRNAs regulated downstream FOXM1 signaling. These results will be beneficial for evaluating nephrotoxicity in chemical risk assessment and for developing new biomarkers to predict nephrotoxicity.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Comprehensive expression analysis of mRNA and microRNA for the investigation of compensatory mechanisms in the rat kidney after unilateral nephrectomy

Matsushita

Toyoda

Yamada

et al. 2020

J of Applied Toxicology

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“…Also, SETD3 methylates FoxM1 and negatively regulates the expression of Vascular Endothelial Growth Factor (VEGF) under normoxia conditions 21 , a known factor related to angiogenesis and tumor progression 58 . On the other hand, FoxM1 has an important role in cancer because its overexpression has been found to be related to poor prognosis in patients 29 . In our study, we found that the expression of FoxM1 also correlated with worse RFS in breast cancer patients ( Table 2).…”

Section: Discussionmentioning

confidence: 99%

SETD3 acts as a prognostic marker in breast cancer patients and modulates the viability and invasion of breast cancer cells

Hassan

Rutsch

Győrffy

et al. 2020

Sci Rep

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In several carcinomas, the SET Domain Containing 3, Actin Histidine Methyltransferase (SETD3)is associated with oncogenesis. However, there is little knowledge about the role of SETD3 in the progression and prognosis of breast cancer. In this study, we first analyzed the prognostic value of SETD3 in breast cancer patients using the database of the public Kaplan-Meier plotter. Moreover, in vitro assays were performed to assess the role of SETD3 in the viability and capacity of invasion of human breast cancer cell lines. We observed that the high expression of SETD3 was associated with better relapse-free survival (RFS) of the whole collective of 3,951 patients, of Estrogen Receptorpositive, and of Luminal A-type breast cancer patients. However, in patients lacking expression of estrogen-, progesterone-and HER2-receptor, and those affected by a p53-mutation, SETD3 was associated with poor RFS. In vitro analysis showed that SETD3 siRNA depletion affects the viability of triple-negative cells as well as the cytoskeletal function and capacity of invasion of highly invasive MDA-MB-231 cells. Interestingly, SETD3 regulates the expression of other genes associated with cancer such as β-actin, FOXM1, FBXW7, Fascin, eNOS, and MMP-2. Our study suggests that SETD3 expression can act as a subtype-specific biomarker for breast cancer progression and prognosis.MTT proliferation assay. SETD3 depleted cells or controls (5 × 10 3 ) were plated in 96-well plates with DMEM medium (without phenol red) (Gibco ® , cat. No. 31053028, Germany) with FCS and incubated for 96 hours. After the incubation time, the medium was removed completely and cells were incubated with 20 µl/well of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) (cat. No. M2128-1G), at 5 mg/ml for 4 hours, at 37 °C. Subsequently, 100 µl of Stopping buffer, pH 4.7 composed of 10% (w/v) sodium dodecyl sulfate (SDS) (cat. No. 3599286) and 50% (v/v) N,) was added to stop the reaction and dissolve the formazan crystals. The absorbance was measured in a VersaMax ® Microplate Reader (Molecular Devices, Sunnyvale, CA, USA) at a wavelength of 595 nm. The proliferation of the control cells was defined as 100%. Results were derived from three independent sets of triplicate experiments. MTT, SDS, and N,N-Dimethyl formamide were from Sigma-

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“…In ATRT, studies have identified a population of cells expressing CD133 with cancer stem cell-like properties that are also resistant to ionizing radiation and have increased radiosensitivity [41,42]. FOXM1 is also closely tied to cancer cell stem cell properties such as cell proliferation, self-renewal, and tumorigenesis [62][63][64][65][66]. In glioblastoma, inhibition of FOXM1 sensitized tumors to irradiation in vitro and in vivo [67].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Dual Class I Histone Deacetylase and Lysine Demethylase Inhibitor Domatinostat (4SC-202) on Growth and Cellular and Genomic Landscape of Atypical Teratoid/Rhabdoid

Hoffman

Zylla

Bhattacharya

et al. 2020

Cancers

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Central nervous system atypical teratoid/rhabdoid tumors (ATRTs) are rare and aggressive tumors with a very poor prognosis. Current treatments for ATRT include resection of the tumor, followed by systemic chemotherapy and radiation therapy, which have toxic side effects for young children. Gene expression analyses of human ATRTs and normal brain samples indicate that ATRTs have aberrant expression of epigenetic markers including class I histone deacetylases (HDAC’s) and lysine demethylase (LSD1). Here, we investigate the effect of a small molecule epigenetic modulator known as Domatinostat (4SC-202), which inhibits both class I HDAC’s and Lysine Demethylase (LSD1), on ATRT cell survival and single cell heterogeneity. Our findings suggest that 4SC-202 is both cytotoxic and cytostatic to ATRT in 2D and 3D scaffold cell culture models and may target cancer stem cells. Single-cell RNA sequencing data from ATRT-06 spheroids treated with 4SC-202 have a reduced population of cells overexpressing stem cell-related genes, including SOX2. Flow cytometry and immunofluorescence on 3D ATRT-06 scaffold models support these results suggesting that 4SC-202 reduces expression of cancer stem cell markers SOX2, CD133, and FOXM1. Drug-induced changes to the systems biology landscape are also explored by multi-omics enrichment analyses. In summary, our data indicate that 4SC-202 has both cytotoxic and cytostatic effects on ATRT, targets specific cell sub-populations, including those with cancer stem-like features, and is an important potential cancer therapeutic to be investigated in vivo.

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Regulation of the master regulator FOXM1 in cancer

Cited by 301 publications

References 137 publications

Comprehensive expression analysis of mRNA and microRNA for the investigation of compensatory mechanisms in the rat kidney after unilateral nephrectomy

Comprehensive expression analysis of mRNA and microRNA for the investigation of compensatory mechanisms in the rat kidney after unilateral nephrectomy

SETD3 acts as a prognostic marker in breast cancer patients and modulates the viability and invasion of breast cancer cells

Analysis of Dual Class I Histone Deacetylase and Lysine Demethylase Inhibitor Domatinostat (4SC-202) on Growth and Cellular and Genomic Landscape of Atypical Teratoid/Rhabdoid

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