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IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner [IGF2BP1 and SRF KD in ES-2 (total RNA)]

ABSTRACT: IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner [IGF2BP1 and SRF KD in ES-2 (total RNA)]

PROVIDER: PRJNA476934 | ENA |

REPOSITORIES: ENA

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IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner [IGF2BP1 and SRF KD in ES-2 (total RNA)]

Project description:The oncofetal mRNA-binding protein IGF2BP1 and the transcriptional regulator SRF modulate gene expression in cancer. In cancer cells, we demonstrate that IGF2BP1 promotes the expression of SRF in a conserved and N6-methyladenosine (m6A) dependent manner by impairing the miRNA-directed decay of the SRF mRNA. This results in enhanced SRF-dependent transcriptional activity and promotes tumor cell growth and invasion. At the post-transcriptional level, IGF2BP1 sustains the expression of various SRF-target genes. The majority of these SRF/IGF2BP1-enhanced genes, including PDLIM7 and FOXK1, shows conserved upregulation with SRF and IGF2BP1 synthesis in cancer. PDLIM7 and FOXK1 promote tumor cell growth and were reported to enhance cell invasion. Consistently, 35 SRF/IGF2BP1-dependent genes showing conserved association with SRF and IGF2BP1 expression indicate a poor overall survival probability in ovarian, liver and lung cancer. In conclusion, these findings identify the SRF/IGF2BP1-, miRNome- and m6A-dependent control of gene expression as a conserved oncogenic driver network in cancer.

2018-10-10 | GSE116059 | GEO

IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner [miRNA-seq]

2018-10-10 | GSE116179 | GEO

IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner [Huh-7]

2018-10-10 | GSE116133 | GEO

IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner

Project description:IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner

| PRJNA477355 | ENA

IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner [Huh-7]

Project description:IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner [Huh-7]

| PRJNA477360 | ENA

IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner [miRNA-seq]

Project description:IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner [miRNA-seq]

| PRJNA477554 | ENA

IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner.

Project description: Not available

| S-EPMC6326824 | biostudies-literature

SRF-VP16 overexpression in ES cells

Project description:Empty vector, SRF-dM-VP16 (control construct lacking the SRF DNA binding domain), or SRF-VP16 were expressed in wild-type ES cells (E14wt), SRF heterozygotes (E99-/+) or two SRF ko cell lines (E81-/-,E100-/-). RNA was harvested 72h after transfection. Each condition was performed in duplicate, except E100-/- vector transfected. Keywords: ordered

2004-11-15 | GSE1948 | GEO

Tumor suppressive function of IGF2BP1 in gastric cancer through decreasing MYC

Project description:Gastric cancer is one of the most common causes of cancer-related death worldwide. The N6-methyladenosine (m6A) reader IGF2BP1 (insulin-like growth factor-2 mRNA binding protein 1) has been reported to promote cancer progression by stabilizing oncogenic mRNAs through its m6A-binding activity in some tumors. However, the role of IGF2BP1 in gastric carcinogenesis remains unclear. In this study, we find that IGF2BP1 is significantly downregulated in tumor tissues from patients with gastric cancer. Lower expression of IGF2BP1 is associated with poor prognosis. IGF2BP1 suppresses gastric cancer cell proliferation in an m6A-dependent manner. Additionally, IGF2BP1 is able to significantly attenuate tumor growth of gastric cancer cells. Further m6A sequencing and m6A-RIP (RNA immunoprecipitation) assays show that MYC (c-myc proto-oncogene) mRNA is a target transcript of IGF2BP1 in gastric cancer cells. IGF2BP1 inhibits gastric cancer cell proliferation by reducing the mRNA and protein expression of MYC. Mechanistically, IGF2BP1 promotes the degradation of MYC mRNA and inhibits its translation efficiency. Taken together, these data suggest that IGF2BP1 plays a tumor-suppressive role in gastric carcinogenesis by downregulating MYC in an m6A-dependent manner, thereby making the IGF2BP1-MYC axis a potential target for gastric cancer treatment.

2024-02-26 | GSE243617 | GEO

IGF2BP1 is a druggable, post-transcriptional super-enhancer of E2F-driven gene expression hallmark in cancer [IGF2BP1 KD in MV3 (total RNA)]

Project description:The IGF2 mRNA-binding protein 1 (IGF2BP1) is a post-transcriptional enhancer of tumor growth. However, conserved effector pathway(s) and the feasibility of targeting IGF2BP1 in cancer cells remained elusive. We demonstrate that IGF2BP1 is a conserved regulator of E2F-driven gene expression and cancer cell cycle progression. IGF2BP1 promotes positive regulators of G1/S transition by stabilizing the respective mRNAs. This regulation is 3’UTR-, miRNA- and m6A-dependent, suggesting a conserved role of m6A-enhanced cell cycle progression across cancers. IGF2BP1 stabilizes E2F-encoding mRNAs and some of their target transcripts revealing a post-transcriptional super-enhancer role of the protein in E2F-driven gene expression. The small molecule BTYNB disrupts this super-enhancer function by impairing IGF2BP1-RNA association and consequently interferes with tumor cell proliferation and tumor growth.

2020-06-17 | GSE146803 | GEO

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