Elevated expression of the <i>IGF2</i> mRNA binding protein 2 (IGF2BP2/IMP2) is linked to short survival and metastasis in esophageal adenocarcinoma

Barghash, Ahmad; Golob-Schwarzl, Nicole; Helms, Volkhard; Haybaeck, Johannes; Kessler, Sonja M.

doi:10.18632/oncotarget.10439

Cited by 54 publications

(53 citation statements)

References 29 publications

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“…A study had also reported that IGF2BP2 in acute lymphoblastic leukemia (ALL) is higher than in healthy donor bone marrow and peripheral blood, while IGF2BP1 and IGF2BP3 is downregulated in ALL [25]. More importantly, IGF2BP2 can serve as a prognostic indicator in several types of solid tumors, including esophageal adenocarcinoma, esophageal squamous carcinoma and glioblastoma [10,24]. Consistent with these data, we found that IGF2BP2 is overexpressed in primary AML patients and patient cohort datasets.…”

Section: Discussionsupporting

confidence: 87%

“…IGF2BP2 has also been suggested to be upregulated in many solid cancers, and it plays an important role in promoting the growth, migration and metastasis of cancer [9,10,[21][22][23][24]. However, the role of IGF2BP2 in AML has not been investigated systematically.…”

Section: Discussionmentioning

confidence: 99%

“…Given the connection between high IGF2BP2 expression and AML prognosis, we then tested the role of IGF2BP2 in AML cell lines. Based on the GO and KEGG analyses of more than 60 esophageal adenocarcinoma patients, it has been reported that IGF2BP2 is significantly associated with proliferation and growth [10]. In addition, a recent study reported that the knockdown of IGF2BP2 expression in colorectal cancer cells suppressed cell growth [31].…”

Section: Discussionmentioning

confidence: 99%

“…IGF2BP2 has been recently reported to be overexpressed in several types of solid cancers [9,10]. IGF2BP2 overexpression promotes glioblastoma multiforme (GBM) progression by activating the IGF2/PI3K/Akt pathway and makes GBM resistant to temozolomide treatment [11].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, IGF2BP2 promotes hepatocarcinogenesis by inducing inflammation [12]. Moreover, elevated IGF2BP2 is associated with poor survival in esophageal adenocarcinoma and basal-like breast cancer patients [9,10]. Therefore, IGF2BP2 is a potential oncogene and prognostic marker in solid cancers.…”

Section: Introductionmentioning

confidence: 99%

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IGF2BP2 Overexpression Indicates Poor Survival in Patients with Acute Myelocytic Leukemia

Liang

et al. 2018

Cell Physiol Biochem

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Background/Aims: IGF2BP2 has been reported to serve as an oncogene in various solid cancers. However, the role of IGF2BP2 in acute myelocytic leukemia (AML) is still unknown. Methods: Public databases Gene Omnibus was used to evaluate the expression of IGF2BP2 in AML patients and healthy controls. In addition, primary cells from these two populations were prepared by Ficoll density centrifugation. Rt-qPCR and western blot were used to detect IGF2BP2 expression in the primary cells from these two populations. Meta-analysis was performed to evaluate the association of IGF2BP2 and prognosis. Lentivirus-based shRNAs were used to knock down IGF2BP2 in AML cell lines KG-1a and Kasumi. Results: We searched the public database Gene Omnibus and analyzed IGF2BP2 expression in both AML and healthy populations. The results showed that IGF2BP2 was overexpressed in AML patients. To verify this phenomenon in fresh human samples, we compared the expression of IGF2BP2 in primary cells from 10 AML patients and 10 healthy controls and found that the expression of IGF2BP2 was upregulated in AML primary cells. More importantly, we observed that IGF2BP2 expression was negatively correlated with the CEBPA mutation status, which is an indicator of good prognosis (RR=0.648, p=0.0001). In addition, IGF2BP2 expression was positively associated with poor prognostic factors, such as the FLT3-ITD mutation (RR=1.198, p=0.0009) and IDH1 mutation (RR=1.354, p=0.0003), as well as intermediate and poor cytogenetic risk (RR=1.214, p=0.0026). To evaluate the prognostic value of IGF2BP2 in AML, we further performed a meta-analysis of 8 studies consisting of 1731 patients and found that IGF2BP2 overexpression was correlated with worse overall survival in AML patients [HR=1.31(1.16-1.49); p = 0.00]. Furthermore, we performed Gene Omnibus and Gene Set Enrichment analyses and found that the genes regulated by IGF2BP2 were mainly enriched in cell proliferation. IGF2BP2 knockdown by 4 different shRNA vectors significantly inhibited the growth of two AML cell lines, KG-1a and Kasumi. Conclusion: Thus, IGF2BP2 may serve as a biomarker to predict the prognosis of AML and as a potential target in AML.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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IGF2BP2 Overexpression Indicates Poor Survival in Patients with Acute Myelocytic Leukemia

Liang

et al. 2018

Cell Physiol Biochem

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Diverse roles of RNA‐binding proteins in cancer traits and their implications in gastrointestinal cancers

Masuda

Kuwano

2018

WIREs RNA

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Gene expression patterns in cancer cells are strongly influenced by posttranscriptional mechanisms. RNA-binding proteins (RBPs) play key roles in posttranscriptional gene regulation; they can interact with target mRNAs in a sequence-and structure-dependent manner, and determine cellular behavior by manipulating the processing of these mRNAs. Numerous RBPs are aberrantly deregulated in many human cancers and hence, affect the functioning of mRNAs that encode proteins, implicated in carcinogenesis. Here, we summarize the key roles of RBPs in posttranscriptional gene regulation, describe RBPs disrupted in cancer, and lastly focus on RBPs that are responsible for implementing cancer traits in the digestive tract. These evidences may reveal a potential link between changes in expression/function of RBPs and malignant transformation, and a framework for new insights and potential therapeutic applications.

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Histochemical evidence of IGF2 mRNA-binding protein 2-mediated regulation of osteoclast function and adhesive ability

Liu

et al. 2018

Histochem Cell Biol

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Insulin-like growth factor 2 (IGF2) messenger RNA-binding proteins (IMPs) are a family of oncofetal RNA-binding proteins that play important roles in cell migration, renewal, and metabolism. IMP2 gene expression may be important in determining IGF2 levels and might, thereby, be central to bone metabolism. In our present study, IMP2-deficient mice exhibited more immature bone structures, characterized by abundant residual cartilage cores; growth plates containing more rich cartilage matrix, which was arranged irregularly; and a significantly thicker hypertrophic chondrocyte layer in the femoral metaphysis, compared with wild-type mice. These abnormalities were associated with profound effects on the size and morphology of osteoclasts. Specifically, the osteoclasts exhibited various polymorphisms, failed to form resorption lacunae, and were detached from the bone surface. Consistent with these findings, IMP2 deficiency reduced the expression of two important proteases (cathepsin K and matrix metallopeptidase 9) as well as that of C-SRC, a critical regulator of ruffled border formation in osteoclasts, indicating impaired osteoclastic activity. IMP2-deficient mice also displayed inhibited osteoclast adhesion owing to defects in the CD44-osteopontin signaling pathway. In summary, we used IMP2-deficient mice as a model to determine whether IMP2 plays a role during bone metabolism. Our results indicate that IMP2 deficiency delayed bone remodeling by significantly inhibiting the activity of osteoclasts and impairing their adhesion.

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Elevated expression of the IGF2 mRNA binding protein 2 (IGF2BP2/IMP2) is linked to short survival and metastasis in esophageal adenocarcinoma

Cited by 54 publications

References 29 publications

IGF2BP2 Overexpression Indicates Poor Survival in Patients with Acute Myelocytic Leukemia

IGF2BP2 Overexpression Indicates Poor Survival in Patients with Acute Myelocytic Leukemia

Diverse roles of RNA‐binding proteins in cancer traits and their implications in gastrointestinal cancers

Histochemical evidence of IGF2 mRNA-binding protein 2-mediated regulation of osteoclast function and adhesive ability

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