Increased IGF2BP3 expression promotes the aggressive phenotypes of colorectal cancer cells in vitro and vivo

Xu, Weimin; Sheng, Yaru; Guo, Yao; Huang, Zhenyu; Huang, Yiji; Wen, Dongpeng; Liu, Chenying; Cui, Long; Yang, Yili; Du, Peng

doi:10.1002/jcp.28483

Cited by 60 publications

(59 citation statements)

References 27 publications

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“…Being a significant RBP, IGF2BP3 is involved in the process of mRNA metabolism and contributes to the cell proliferation and invasion in various cancers ( Samanta et al, 2012 ; Taniuchi et al, 2014 ; Hsu et al, 2015 ; Palanichamy et al, 2016 ; Zhang et al, 2017 ; Xu et al, 2019 ). Moreover, multiple evidences proved that IGF2BP3 is relate to the processes of cancer development and prognosis ( Lochhead et al, 2012 ; Cao et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…A growing body of evidence shows that IGF2BP3 has shown its promising value on cancer therapy ( Lochhead et al, 2012 ; Hsu et al, 2015 ). Numerous cancers have been identified the overexpression of IGF2BP3 including lung cancer ( Findeis-Hosey and Xu, 2012 ), breast cancer ( Scott et al, 2018 ), colorectal cancer ( Wei et al, 2017 ; Xu et al, 2019 ), hepatocellular carcinoma ( Shaalan et al, 2018 ), pancreatic cancer ( Chen et al, 2019 ), glioblastoma and ovarian clear cell carcinoma ( Bi et al, 2016 ; Dutoit et al, 2018 ). IGF2BP3 is a carcinoembryonic protein that is highly expressed during embryogenesis, lowly expressed in adult tissues, and re-expressed in malignant tissues ( Palanichamy et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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IGF2BP3 May Contributes to Lung Tumorigenesis by Regulating the Alternative Splicing of PKM

Huang

Zhang

Jiang

et al. 2020

Front. Bioeng. Biotechnol.

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RNA binding proteins (RBPs) play a key role in genome regulation. Here we report the post-transcript regulation of IGF2BP3, which belongs to the insulin-like growth factor 2 mRNA binding protein family. We used iRIP-seq and RNA-seq to analyze the transcript regulation and alternative splicing on IGF2BP3 treated with overexpression cells and control. Overexpressed IGF2BP3 has broadly increased genes expression which involved in G-protein coupled receptor signaling pathway, positive regulation of cell proliferation, and signal transduction. IGF2BP3 regulated alternative splicing of multiple genes mainly clustered at response to hypoxia, negative regulation of transcription, and embryonic development. This study first provides alternative splicing analysis on transcription level of IGF2BP3 regulation, which laid the foundation for later research on IGF2BP3 critical functions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

IGF2BP3 May Contributes to Lung Tumorigenesis by Regulating the Alternative Splicing of PKM

Huang

Zhang

Jiang

et al. 2020

Front. Bioeng. Biotechnol.

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“…Among them, IGF2BP3 was demonstrated as a predictor of progression as well as poor survival in colon cancer [11]. Overexpression of IGF2BP3 also promoted the invasion of colon cancer in both vivo and vitro [12]. However, the m6A reader role of IGF2BP3 in colon cancer remains unclear.…”

Section: Introductionmentioning

confidence: 99%

RNA N6-methyladenosine reader IGF2BP3 regulates cell cycle and angiogenesis in colon cancer

Yang

Wang

et al. 2020

J Exp Clin Cancer Res

194

136

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Background N6-Methyladenosine (m6A) modification has been implicated in multiple processes for colon cancer development. IGF2BP3 was a newly reported m6A reader, whereas its role in colon cancer remains unclear. Methods The expression of m6A associated enzymes and total m6A level were measured by Western Blotting analysis and m6A RNA Methylation Quantification Kit respectively. Cell cycle was analyzed by flowcytometry. The interaction of IGF2BP3 and related targets was analyzed by RNA immunoprecipitation (RIP) and m6A RNA immunoprecipitation (MeRIP) assays. Results We investigated all m6A regulated enzymes in colon cancer and found only the overexpression of IGF2BP3 was associated with cancer progression and survival based on The Cancer Genome Atlas (TCGA) databases. Additionally, we also demonstrated IGF2BP3 was associated with DNA replication in the cell cycle. Knockdown of IGF2BP3 significantly repressed percentage of S phase of cell cycle as well as cell proliferation. Further research demonstrated IGF2BP3 bound to the mRNA of Cyclin D1 (CCND1, checkpoint of G1/S phase of cell cycle) and reduced its mRNA stability via reading m6A modification in the CDS region. Overexpression of Cyclin D1 in IGF2BP3 down-regulated cells completely rescued the inhibited percentage of S phase in cell cycle as well as cell proliferation. Additionally, we also demonstrated a similar role of IGF2BP3 at VEGF. IGF2BP3 bound to the mRNA of VEGF and reads m6A modification, thus regulated both expression and stability of VEGF mRNA. Knockdown of IGF2BP3 repressed angiogenesis in colon cancer via regulating VEGF. Conclusion Knockdown of IGF2BP3 repressed DNA replication in the S phase of cell cycle and angiogenesis via reading m6A modification of CCND1 and VEGF respectively. IGF2BP3 was a possible prognosis marker and potential therapeutic target of colon cancer.

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“…Moreover, its biological roles in liver cancer [35], head and neck squamous cell carcinoma [13], and lung cancer [36] were determined. Finally, IGF2BP3 plays significant biological roles in thyroid cancer [37], breast cancer [38], gastric cancer [39], and colorectal cancer [40]. However, the above three m6A regulators have not been reported in UCEC.…”

Section: Discussionmentioning

confidence: 98%

Multiomics profile and prognostic gene signature of m6A regulators in uterine corpus endometrial carcinoma

et al. 2020

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Uterine corpus endometrial carcinoma (UCEC) is the most common type of gynecologic malignancy worldwide. Despite advances in the treatments of UCEC, its incidence and mortality rates are still increasing. N6-methyladenosine (m6A) is the most common form of RNA modification and has attracted increasing interest in cancer pathogenesis and progression. Thus, we aimed to identify the landscape of m6A regulators and build a prognostic gene signature in UCEC. In this study, we first analyzed copy number variations (CNVs), single nucleotide variations (SNVs) and gene expression profiles as well as matched clinical information of UCEC patients from The Cancer Genome Atlas (TCGA) database. Next, we determined that CNVs in m6A regulatory genes had a significant negative impact on patient survival. The mRNA expression levels of a total of 16 m6A regulators were significantly correlated with different CNV patterns. Using univariate Cox regression analysis, IGF2BP1, KIAA1429, IGF2BP3, YTHDF3, and IGF2BP2 were found to be closely associated with UCEC patient survival outcomes. Based on the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression models, we built a 3-gene (IGF2BP3, KIAA1429 and IGF2BP1) signature of m6A regulators with prognostic value in UCEC that could effectively predict patient prognosis (log-rank test p-value < 0.0001). In addition, risk scores were significantly different between patients stratified by tumor stage, SNV, and CNV. Multivariate Cox regression analysis suggested that risk score might be an independent prognostic indicator for the overall survival of patients with UCEC (p-value < 0.05). Gene enrichment analysis indicated that high IGF2BP1 gene expression is associated with cytoplasmic stress granules. KIAA1429 gene expression is associated with cellular nucleic acid metabolism. The expression of the IGF2BP3 gene is associated with RNA binding processes. In conclusion, we determined that genetic alterations in m6A regulatory genes could be effective and reliable biomarkers for UCEC prognosis prediction.

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Increased IGF2BP3 expression promotes the aggressive phenotypes of colorectal cancer cells in vitro and vivo

Cited by 60 publications

References 27 publications

IGF2BP3 May Contributes to Lung Tumorigenesis by Regulating the Alternative Splicing of PKM

IGF2BP3 May Contributes to Lung Tumorigenesis by Regulating the Alternative Splicing of PKM

RNA N6-methyladenosine reader IGF2BP3 regulates cell cycle and angiogenesis in colon cancer

Multiomics profile and prognostic gene signature of m6A regulators in uterine corpus endometrial carcinoma

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