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Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer

ABSTRACT: Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer

PROVIDER: PRJNA804726 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17904660.fastq.gz	Fastqsanger.gz
	SRR17904661.fastq.gz	Fastqsanger.gz
	SRR17904662.fastq.gz	Fastqsanger.gz
	SRR17904663.fastq.gz	Fastqsanger.gz
	SRR17955970.fastq.gz	Fastqsanger.gz

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Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer [RIP-Seq]

Project description:We reported earlier that IQGAP3 is an important stem cell factor in rapidly proliferating isthmus stem cells in the stomach. Furthermore, we observed robust induction of IQGAP3 expression in terminally differentiated chief cells and de-differentiated cells following tissue damage. The elevated expression of IQGAP3 in cancer and its association with metastasis suggest a fundamental role for IQGAP3 in proliferating cancer stem cells. What causes the upregulation of IQGAP3 in cancer is unclear. Here, we show that IGF2BP1 and IQGAP3 expression levels are highest in the blastocyst, with both showing decreases during adulthood. This suggests that IQGAP3, like IGF2BP1, is an early developmental gene that is aberrantly upregulated upon reexpression of IGF2BP1 during carcinogenesis. We found that IGF2BP1 binds and stabilizes m 6 A-modified IQGAP3 transcripts. Furthermore, downstream targets of IGF2BP1, namely SRF and FOXM1, also upregulate IQGAP3 expression. These multiple layers of IQGAP3 regulation, which may safeguard against inappropriate stem cell proliferation, present additional drug targets to inhibit IQGAP3-driven malignant growth.

2022-09-16 | GSE196238 | GEO

Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer [RNA-Seq]

2022-09-16 | GSE196405 | GEO

Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer [RNA-Seq]

Project description:Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer [RNA-Seq]

| PRJNA804748 | ENA

Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer [RIP-Seq]

Project description:Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer [RIP-Seq]

| PRJNA803993 | ENA

Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer

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

2022-09-16 | GSE196406 | GEO

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

The Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homeostasis and repair [SMART-SeqII]

Project description:Objective: Tissue stem cells are central regulators of organ homeostasis. We looked for a protein that is exclusively expressed and functionally involved in stem cell activity in rapidly proliferating isthmus stem cells in the stomach corpus. Design: We uncovered the specific expression of Iqgap3 in proliferating isthmus stem cells through immunofluorescence and in situ hybridization. We performed lineage tracing and transcriptomic analysis of Iqgap3+ isthmus stem cells with the Iqgap3-2A-tdTomato mouse model. Depletion of Iqgap3 revealed its functional importance in maintenance and proliferation of stem cells. We further studied Iqgap3 expression and the associated gene expression changes during tissue repair after tamoxifen-induced damage. Immunohistochemistry revealed elevated expression of Iqgap3 in proliferating regions of gastric tumors from patient samples. Results: Iqgap3 is a highly specific marker of proliferating isthmus stem cells during homeostasis. Iqgap3+ isthmus stem cells give rise to major cell types of the corpus unit. Iqgap3 expression is essential for the maintenance of stem potential. The Ras pathway is a critical partner of Iqgap3 in promoting strong proliferation in isthmus stem cells. The robust induction of Iqgap3 expression following tissue damage indicates an active role for Iqgap3 in tissue regeneration. Conclusion: IQGAP3 is a major regulator of stomach epithelial tissue homeostasis and repair. The upregulation of IQGAP3 in gastric cancer suggests that IQGAP3 plays an important role in cancer cell proliferation.

2021-03-08 | GSE161443 | GEO

The Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homeostasis and repair [RNA-Seq]

2021-03-08 | GSE161442 | 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 [miRNA-seq]

2018-10-10 | GSE116179 | GEO