RNA-binding protein IGF2BP1 is required for spermatogenesis in an age-dependent manner
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE275200 | GEO | 2024/08/24
REPOSITORIES: GEO
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Project description:Post-transcriptional regulation mediated by RNA binding proteins is crucial for male germline development. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), an RNA binding protein, is specifically expressed in human and mouse male gonads and is involved in manifold biological processes and tumorigenesis. However, the function of IGF2BP1 in mammalian spermatogenesis remains poorly understood. Herein, we generated an Igf2bp1 conditional knockout mouse model using Nanos3-Cre. Germ cell deficiency of Igf2bp1 in mice caused spermatogenic defects in an age-dependent manner, resulting in decreased numbers of undifferentiated spermatogonia and increased germ cell apoptosis. Immunoprecipitation-mass spectrometry analysis revealed that ELAV-like RNA binding protein 1, a well-recognized mRNA stabilizer, interacted with IGF2BP1. Single cell RNA-sequencing showed distinct mRNA profiles in spermatogonia from conditional knockout versus wide type mice. Further research showed that IGF2BP1 plays a vital role in the modulation of spermatogenesis by regulating Lin28a mRNA, which is essential for clonal expansion of undifferentiated spermatogonia. Thus, our results highlight the crucial effects of IGF2BP1 on spermatogonia for the long-term maintenance of spermatogenesis
2024-09-03 | GSE276205 | GEO
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
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 | GSE116179 | GEO
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 | GSE116133 | GEO
Project description:Our study demonstrated that the expression of Igf2bp1 in activated microglia was significantly up-regulated, implying a role of Igf2bp1 in LPS-induced m6A modifications in microglia. To understand the roles of Igf2bp1 on LPS-induced m6A modification in microglia, we performed Igf2bp1 loss-of-function (LOF) approach. Microglia stimulated by LPS were transfected with either scrambled siRNA control or Igf2bp1 siRNA for 48 hours. To m6A modification profiles in control and Igf2bp1 LOF microglia were determined by MeRIP-seq analysis.
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Project description:The IGF2 mRNA binding protein 1 (IGF2BP1) promotes tumor progression in a multitude of solid tumors and its expression is associated with adverse prognosis. The main role proposed for IGF2BP1 in cancer cells is the stabilization of mRNAs encoding pro-oncogenic factors. Several binding studies, however, revealed a plethora of putative IGF2BP1-RNA targets. Thus, at present the main, conserved target RNAs and pathways controlled by IGF2BP1 in cancer remain elusive. In this study, we present a set of genes showing a conserved pattern of deregulation in dependence of IGF2BP1 expression in cancer-derived cell lines. By incorporating publicly available data sets, we further compiled a set of RNAs probably stabilized by IGF2BP1 in cancer and characterized them. Functional enrichment analyses revealed conserved pathways influenced by IGF2BP1 in cancer.
2021-03-22 | GSE161099 | GEO
Project description:The IGF2 mRNA binding protein 1 (IGF2BP1) promotes tumor progression in a multitude of solid tumors and its expression is associated with adverse prognosis. The main role proposed for IGF2BP1 in cancer cells is the stabilization of mRNAs encoding pro-oncogenic factors. Several binding studies, however, revealed a plethora of putative IGF2BP1-RNA targets. Thus, at present the main, conserved target RNAs and pathways controlled by IGF2BP1 in cancer remain elusive. In this study, we present a set of genes showing a conserved pattern of deregulation in dependence of IGF2BP1 expression in cancer-derived cell lines. By incorporating publicly available data sets, we further compiled a set of RNAs probably stabilized by IGF2BP1 in cancer and characterized them. Functional enrichment analyses revealed conserved pathways influenced by IGF2BP1 in cancer.
2021-03-22 | GSE161086 | GEO
Project description:The IGF2 mRNA binding protein 1 (IGF2BP1) promotes tumor progression in a multitude of solid tumors and its expression is associated with adverse prognosis. The main role proposed for IGF2BP1 in cancer cells is the stabilization of mRNAs encoding pro-oncogenic factors. Several binding studies, however, revealed a plethora of putative IGF2BP1-RNA targets. Thus, at present the main, conserved target RNAs and pathways controlled by IGF2BP1 in cancer remain elusive. In this study, we present a set of genes showing a conserved pattern of deregulation in dependence of IGF2BP1 expression in cancer-derived cell lines. By incorporating publicly available data sets, we further compiled a set of RNAs probably stabilized by IGF2BP1 in cancer and characterized them. Functional enrichment analyses revealed conserved pathways influenced by IGF2BP1 in cancer.
2021-03-22 | GSE161087 | GEO
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
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