Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gfi1 upregulates c-Myc expression and promotes c-Myc-driven cell proliferation

ABSTRACT: Gfi1 is a zinc-finger transcriptional repressor that plays an important role in hematopoiesis. When aberrantly activated, Gfi1 may function as a weak oncoprotein in the lymphoid system, but collaborates strongly with c-Myc in lymphomagenesis. The mechanism by which Gfi1 collaborates with c-Myc in lymphomagenesis is incompletely understood. We show here that Gfi1 augmented the expression of c-Myc protein in cells transfected with c-Myc expression constructs. The N-terminal SNAG domain and C-terminal ZF domains of Gfi1, but not its transcriptional repression and DNA binding activities, were required for c-Myc upregulation. We further show that Gfi1 overexpression led to reduced polyubiquitination and increased stability of c-Myc protein. Interestingly, the levels of endogenous c-Myc mRNA and protein were augmented upon Gfi1 overexpression, but reduced following Gfi1 knockdown or knockout, which was associated with a decline in the expression of c-Myc-activated target genes. Consistent with its role in the regulation of c-Myc expression, Gfi1 promoted Myc-driven cell cycle progression and proliferation. Together, these data reveal a novel mechanism by which Gfi1 augments the biological function of c-Myc and may have implications for understanding the functional collaboration between Gfi1 and c-Myc in lymphomagenesis.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7554040 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Inactivation of Ezh2 Upregulates Gfi1 and Drives Aggressive Myc-Driven Group 3 Medulloblastoma.

Project description:The most aggressive of four medulloblastoma (MB) subgroups are cMyc-driven group 3 (G3) tumors, some of which overexpress EZH2, the histone H3K27 mono-, di-, and trimethylase of polycomb-repressive complex 2. Ezh2 has a context-dependent role in different cancers as an oncogene or tumor suppressor and retards tumor progression in a mouse model of G3 MB. Engineered deletions of Ezh2 in G3 MBs by gene editing nucleases accelerated tumorigenesis, whereas Ezh2 re-expression reversed attendant histone modifications and slowed tumor progression. Candidate oncogenic drivers suppressed by Ezh2 included Gfi1, a proto-oncogene frequently activated in human G3 MBs. Gfi1 disruption antagonized the tumor-promoting effects of Ezh2 loss; conversely, Gfi1 overexpression collaborated with Myc to bypass effects of Trp53 inactivation in driving MB progression in primary cerebellar neuronal progenitors. Although negative regulation of Gfi1 by Ezh2 may restrain MB development, Gfi1 activation can bypass these effects.

| S-EPMC5415387 | biostudies-literature

Inactivation of Ezh2 upregulates Gfi1 and drives aggressive Myc-driven Group 3 medulloblastoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-03-01 | GSE84762 | GEO

GFI1 promotes the proliferation and migration of esophageal squamous cell carcinoma cells through the inhibition of SOCS1 expression.

Project description:Growth factor‑independent 1 (GFI1) has been reported to serve a vital role in hematopoietic development. However, the function and molecular mechanism of GFI1 in esophageal squamous cell carcinoma (ESCC) remains unknown. In the present study, the biological functions and the molecular mechanism of the effects of GFI1 in ESCC were analyzed. The results demonstrated that GFI1 expression levels were significantly upregulated in ESCC compared with those in normal esophageal tissues. Knockdown of GFI1 using small interfering RNA suppressed ESCC cell proliferation and migration. Furthermore, GFI1 enhanced STAT3 and NF‑κB signaling by inhibiting the expression of suppressor of cytokine signaling 1 (SOCS1) in ESCC cells. Taken together, the results of the present study demonstrated that GFI1 promoted the proliferation and migration of ESCC cells via inhibition of SOCS1 expression. These results suggested that GFI1 may be a valuable target for ESCC therapy.

| S-EPMC8416140 | biostudies-literature

Inactivation of Ezh2 upregulates Gfi1 and drives aggressive Myc-driven Group 3 medulloblastoma [ChIP-Seq]

Project description:The most aggressive of four medulloblastoma (MB) subgroups are cMYC-driven Group 3 (G3) tumors, some of which overexpress EZH2, the histone H3K27 trimethylase of polycomb repressive complex-2. Yet, engineered deletions of Ezh2 in G3 MBs by gene editing nucleases accelerated tumorigenesis, whereas Ezh2 re-expression reversed attendant histone modifications and slowed tumor progression. Candidate oncogenic drivers upregulated following Ezh2 deletion included Gfi1, a proto-oncogene frequently activated in human G3 MBs. Gfi1 disruption antagonized the tumor promoting effects of Ezh2 loss; conversely, Gfi1 overexpression collaborated with Myc to bypass effects of Trp53 inactivation in primary cerebellar neuronal progenitors thereby driving MB progression. Although negative epigenetic regulation of Gfi1 by Ezh2 may restrain MB development, Gfi1 activation can bypass these effects.

2017-03-01 | GSE84761 | GEO

Inactivation of Ezh2 upregulates Gfi1 and drives aggressive Myc-driven Group 3 medulloblastoma [RNA-Seq]

2017-03-01 | GSE84462 | GEO

N6-methyladenosine methyltransferase METTL3 promotes colorectal cancer cell proliferation through enhancing MYC expression.

Project description:N6-methyladenosine (m6A) modification is the most common chemical modification in eukaryotic mRNA, which plays a crucial role in regulating mRNA stability, splicing, and translation. METTL3 (methyltransferase like 3), a major RNA N6-adenosine methyltransferase, has been reported to participate in the progression of many cancers. However, its function in colorectal cancer (CRC) remains largely unknown. In this study, we revealed that METTL3 played an oncogenic role in CRC. We found that METTL3 was significantly upregulated in CRC, using quantitative real-time PCR, western blotting, and immunohistochemical staining, and upregulation of METTL3 was associated with clinicopathological features. Functionally, knockdown of METTL3 suppressed CRC cell proliferation in vitro and in vivo. In contrast, overexpression of METTL3 promoted the growth of CRC cells both in vitro and in vivo. Mechanistically, METTL3 exerted its function through enhancing MYC expression, at least partially in an m6A-IGF2BP1-dependent manner. In conclusion, we found that METTL3 was frequently upregulated in human CRC and promoted CRC progression though enhancing MYC expression. This provided new insights into the molecular mechanisms underlying the development of colorectal cancer.

| S-EPMC7270026 | biostudies-literature

IFNγ suppresses the expression of GFI1 and thereby inhibits Th2 cell proliferation.

Project description:While IFNγ is a well-known cytokine that actively promotes the type I immune response, it is also known to suppress the type II response by inhibiting the differentiation and proliferation of Th2 cells. However, the mechanism by which IFNγ suppresses Th2 cell proliferation is still not fully understood. We found that IFNγ decreases the expression of growth factor independent-1 transcriptional repressor (GFI1) in Th2 cells, resulting in the inhibition of Th2 cell proliferation. The deletion of the Gfi1 gene in Th2 cells results in the failure of their proliferation, accompanied by an impaired cell cycle progression. In contrast, the enforced expression of GFI1 restores the defective Th2 cell proliferation, even in the presence of IFNγ. These results demonstrate that GFI1 is a key molecule in the IFNγ-mediated inhibition of Th2 cell proliferation.

| S-EPMC8608330 | biostudies-literature

GFI1 promotes gastric cancer cell HS746T proliferation

Project description:To investigate the function of GFI1 in GC, we ectopically expressed GFI1 in HS746T cells and analysised the transciptional data from HS746T GFI1 over-expression cells and wild type cells by human microarray

2019-06-08 | GSE115530 | GEO

CSIG promotes hepatocellular carcinoma proliferation by activating c-MYC expression.

Project description:Cellular senescence-inhibited gene (CSIG) protein significantly prolongs the progression of replicative senescence, but its role in tumorigenesis is unclear. To reveal the role of CSIG in HCC, we determined its expression in HCC tissues and surrounding tissues and its functions in tumor cell proliferation in vitro and in vivo. CSIG protein was overexpressed in 86.4% of the human HCC cancerous tissues as compared with matched surrounding tissues, and its protein expression was greater in HCC cells than the non-transformed hepatic cell line L02. Furthermore, upregulation of CSIG significantly increased the colony formation of SMMC7721 and HepG2 cells, and silencing CSIG could induce cell cycle arrest and cell apoptosis. The tumorigenic ability of CSIG was confirmed in vivo in a mouse xenograft model. Our results showed that CSIG promoted the proliferation of HepG2 and SMMC7721 cells in vivo. Finally, CSIG protein directly interacted with c-MYC protein and increased c-MYC protein levels; the ubiquitination and degradation of c-MYC protein was increased with knockdown of CSIG. CSIG could also increase the expression of c-MYC protein in SMMC7721 cells in vivo, and it was noted that the level of c-MYC protein was also elevated in most human cancerous tissues with high level of CSIG.

| S-EPMC4467111 | biostudies-literature

GFI1 promotes gastric cancer cell HS746T proliferation

Project description:GFI1 promotes gastric cancer cell HS746T proliferation

| PRJNA475274 | ENA