CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis

Huot, Geneviève; Vernier, Mathieu; Bourdeau, Véronique; Doucet, Laurent; Saint-Germain, Emmanuelle; Gaumont-Leclerc, Marie-France; Moro, Alejandro; Ferbeyre, Gerardo

doi:10.1091/mbc.e13-02-0110

Cited by 36 publications

(31 citation statements)

References 39 publications

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“…FOXN3 is a direct target of and is downregulated by miR-574-5p to promote the progression of human lung cancer [18]. Moreover, FOXN3 inhibits cell proliferation by repressing PIM2 and protein biosynthesis [19]. FOXN3 also suppresses the expression of N-cadherin mRNA and protein by transcriptionally repressing N-cadherin promoter activity [20].…”

Section: Discussionmentioning

confidence: 99%

The transcription factor FOXN3 inhibits cell proliferation by downregulating E2F5 expression in hepatocellular carcinoma cells

Sun

et al. 2016

Oncotarget

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Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and the mechanisms underlying the development of HCC remain to be elucidated. Forkhead box N3 (FOXN3) is an important member of the FOX family of transcription factors that plays an essential role in several cancers but has not been investigated in HCC. In this study, we demonstrate that FOXN3 is downregulated in human primary HCC tissues compared with their matched adjacent liver tissues. Functional tests of FOXN3 demonstrated that FOXN3 inhibits the proliferation of HCC cells in vitro and in vivo. Additionally, FOXN3 repressed the mRNA and protein expression of E2F5, a reported potential oncogene, by inhibiting the promoter activity of E2F5. Collectively, our findings indicate that FOXN3 functions as a tumor suppressor in HCC by downregulating the expression of E2F5.

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Section: Discussionmentioning

confidence: 99%

The transcription factor FOXN3 inhibits cell proliferation by downregulating E2F5 expression in hepatocellular carcinoma cells

Sun

et al. 2016

Oncotarget

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“…At the cellular level, FOXN3 was described as a checkpoint suppressor (CHES1) in yeast (5) and was shown to inhibit protein biosynthesis (6) or to downregulate E2F5 in human cells to control cell cycle (7). At the molecular level, although it has been reported that FOXN3 interacts with xSin3/xRPD3 in X. laevis (3) and Sin3 in Saccharomyces cerevisiae (8) and with MEN1 (9) or SKIP (10) in human cells to exert transcriptional repressive function, in Drosophila testes it was demonstrated that FOXN3 acts to activate transcription (11).…”

Section: Introductionmentioning

confidence: 99%

The FOXN3-NEAT1-SIN3A repressor complex promotes progression of hormonally responsive breast cancer

Zhang

Liu

et al. 2017

Journal of Clinical Investigation

170

155

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“…The data from human protein atlas (http://www.proteinatlas.org/) revealed that the protein levels of FOXN3 were upregulated in most cancer tissues. A recent study in a cancer cell line indicated that CHES1/FOXN3 decreases cell proliferation by repressing PIM2 and protein biosynthesis, suggesting that FOXN3 is a potential tumor suppressor [38]. However, we found that overexpression of CHES-1-like in fly testis could prevent early germ cell differentiation and lead to tumor-like structure formation.…”

Section: Discussionmentioning

confidence: 58%

CHES-1-like, the ortholog of a non-obstructive azoospermia-associated gene, blocks germline stem cell differentiation by upregulating Dpp expression inDrosophilatestis

Liu

Xiang

et al. 2016

Oncotarget

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Azoospermia is a high risk factor for testicular germ cell tumors, whose underlying molecular mechanisms remain unknown. In a genome-wide association study to identify novel loci associated with human non-obstructive azoospermia (NOA), we uncovered a single nucleotide polymorphism (rs1887102, P=2.60 ×10−7) in a human gene FOXN3. FOXN3 is an evolutionarily conserved gene. We used Drosophila melanogaster as a model system to test whether CHES-1-like, the Drosophila FOXN3 ortholog, is required for male fertility. CHES-1-like knockout flies are viable and fertile, and show no defects in spermatogenesis. However, ectopic expression of CHES-1-like in germ cells significantly reduced male fertility. With CHES-1-like overexpression, spermatogonia fail to differentiate after four rounds of mitotic division, but continue to divide to form tumor like structures. In these testes, expression levels of differentiation factor, Bam, were reduced, but the expression region of Bam was expanded. Further reduced Bam expression in CHES-1-like expressing testes exhibited enhanced tumor-like structure formation. The expression of daughters against dpp (dad), a downstream gene of dpp signaling, was upregulated by CHES-1-like expression in testes. We found that CHES-1-like could directly bind to the dpp promoter. We propose a model that CHES-1-like overexpression in germ cells activates dpp expression, inhibits spermatocyte differentiation, and finally leads to germ cell tumors.

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CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis

Cited by 36 publications

References 39 publications

The transcription factor FOXN3 inhibits cell proliferation by downregulating E2F5 expression in hepatocellular carcinoma cells

The transcription factor FOXN3 inhibits cell proliferation by downregulating E2F5 expression in hepatocellular carcinoma cells

The FOXN3-NEAT1-SIN3A repressor complex promotes progression of hormonally responsive breast cancer

CHES-1-like, the ortholog of a non-obstructive azoospermia-associated gene, blocks germline stem cell differentiation by upregulating Dpp expression inDrosophilatestis

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