Increased tumor cell proliferation in mantle cell lymphoma is associated with elevated insulin-like growth factor 2 mRNA-binding protein 3 expression

Hartmann, Elena; Beà, Sı́lvia; Navarro, Alba; Trapp, Vanessa; Campo, Elı́as; Ott, German; Rosenwald, Andreas

doi:10.1038/modpathol.2012.84

Cited by 22 publications

(20 citation statements)

References 24 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(B) The same analysis using the epithelial and mesenchymal signatures from the meta-analysis by Groger et al [18]. [35,36]. Our HSC microarray analysis confirmed that expression of Igf1R and Igf2bp1 both increase in parallel with Igf2bp3 as mouse Q-HSC differentiate into MF (Fig.…”

Section: Igf2bp3 Promotes Mf-hsc Growth and Proliferation By Stabilizsupporting

confidence: 62%

RNA Binding Proteins Control Transdifferentiation of Hepatic Stellate Cells into Myofibroblasts

Wang

Jung

Hyun

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Myofibroblasts (MF) derived from quiescent nonfibrogenic hepatic stellate cells (HSC) are the major sources of fibrous matrix in cirrhosis. Because many factors interact to regulate expansion and regression of MF-HSC populations, efforts to prevent cirrhosis by targeting any one factor have had limited success, motivating research to identify mechanisms that integrate these diverse inputs. As key components of RNA regulons, RNA binding proteins (RBPs) may fulfill this function by orchestrating changes in the expression of multiple genes that must be coordinately regulated to affect the complex phenotypic modifications required for HSC transdifferentiation. Methods: We profiled the transcriptomes of quiescent and MF-HSC to identify RBPs that were differentially-expressed during HSC transdifferentiation, manipulated the expression of the most significantly induced RBP, insulin like growth factor 2 binding protein 3 (Igf2bp3), and evaluated transcriptomic and phenotypic effects. Results: Depleting Igf2bp3 changed the expression of thousands of HSC genes, including multiple targets of TGF-β signaling, and caused HSCs to reacquire a less proliferative, less myofibroblastic phenotype. RNA immunoprecipitation assays demonstrated that some of these effects were mediated by direct physical interactions between Igf2bp3 and mRNAs that control proliferative activity and mesenchymal traits. Inhibiting TGF-β receptor-1 signaling revealed a microRNA-dependent mechanism that induces Igf2bp3. Conclusions: The aggregate results indicate that HSC transdifferentiation is ultimately dictated by Igf2bp3-dependent RNA regulons and thus, can be controlled simply by manipulating Igf2bp3.

show abstract

Section: Igf2bp3 Promotes Mf-hsc Growth and Proliferation By Stabilizsupporting

confidence: 62%

RNA Binding Proteins Control Transdifferentiation of Hepatic Stellate Cells into Myofibroblasts

Wang

Jung

Hyun

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Like p53 expression, tumors with high Ki-67 PI more frequently showed IMP3 expression. This observation has been documented in other tumors like hepatocellular carcinoma, B cell lymphoma, meningioma, and bile duct carcinoma 14,27,28,29. With these findings, IMP3 is considered to be a better prognostic marker than p53 or Ki-67 and these three proteins may be closely connected.…”

Section: Discussionmentioning

confidence: 67%

IMP3, a Promising Prognostic Marker in Clear Cell Renal Cell Carcinoma

et al. 2014

View full text Add to dashboard Cite

BackgroundInsulin-like growth factor II mRNA-binding protein 3 (IMP3) has been reported as a prognostic biomarker in various cancers. To validate IMP3 as a prognostic biomarker in renal cell carcinoma (RCC), we investigated the expression of IMP3, p53, and Ki-67, and their associations with clinicopathologic outcomes.MethodsWe studied 148 clear cell RCCs (CCRCCs) from patients who underwent radical nephrectomy. The expression levels of IMP3, p53, and Ki-67 were assessed by immunohistochemical staining and the clinical and pathologic parameters were retrospectively reviewed.ResultsTwenty-nine percent of CCRCCs expressed IMP3. Forty-one percent of IMP3-immunopositive tumors developed metastases, while only 11.4% of IMP3-negative tumors developed metastases (p<.001). A Kaplan-Meier curve showed that patients with IMP3-immunopositive tumors had lower metastasis-free survival and cancer-specific survival than did those with IMP3-immunonegative tumors (p<.001 and p<.001, respectively). Expression of high Ki-67 proliferation index was also associated with a higher metastatic rate. In the multivariate Cox regression analysis, pT stage and IMP3-positivity were independently associated with disease-specific survival.ConclusionsIMP3 is an independent prognostic biomarker for patients with CCRCC to predict metastasis and poor outcome.

show abstract

“…Therefore, it is tempting to speculate that IGF2BP3 is a direct transcriptional target of MLL fusion proteins. However, IGF2BP3 is also overexpressed in most of the B-ALL cell lines tested, various mature B cell neoplasms (34)(35)(36)(37), and a number of epithelial malignancies. Furthermore, differential regulation of this protein has been observed in B-ALL (38).…”

Section: Discussionmentioning

confidence: 99%

RNA-binding protein IGF2BP3 targeting of oncogenic transcripts promotes hematopoietic progenitor proliferation

Palanichamy¹,

Tran²,

Howard³

et al. 2016

Journal of Clinical Investigation

139

193

View full text Add to dashboard Cite

Posttranscriptional control of gene expression is important for defining both normal and pathological cellular phenotypes. In vitro, RNA-binding proteins (RBPs) have recently been shown to play important roles in posttranscriptional regulation; however, the contribution of RBPs to cell specification is not well understood. Here, we determined that the RBP insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is specifically overexpressed in mixed lineage leukemia-rearranged (MLLrearranged) B-acute lymphoblastic leukemia (B-ALL), which constitutes a subtype of this malignancy associated with poor prognosis and high risk of relapse. IGF2BP3 was required for the survival of B-ALL cell lines, as knockdown led to decreased proliferation and increased apoptosis. Enforced expression of IGF2BP3 provided murine BM cells with a strong survival advantage, led to proliferation of hematopoietic stem and progenitor cells, and skewed hematopoietic development to the B cell/myeloid lineage. Cross-link immunoprecipitation and high throughput sequencing uncovered the IGF2BP3-regulated transcriptome, which includes oncogenes MYC and CDK6 as direct targets. IGF2BP3 regulated transcripts via targeting elements within 3' untranslated regions (3'UTR), and enforced IGF2BP3 expression in mice resulted in enhanced expression of Myc and Cdk6 in BM. Together, our data suggest that IGF2BP3-mediated targeting of oncogenic transcripts may represent a critical pathogenetic mechanism in MLL-rearranged B-ALL and support IGF2BP3 and its cognate RNA-binding partners as potential therapeutic targets in this diseas

show abstract

Increased tumor cell proliferation in mantle cell lymphoma is associated with elevated insulin-like growth factor 2 mRNA-binding protein 3 expression

Cited by 22 publications

References 24 publications

RNA Binding Proteins Control Transdifferentiation of Hepatic Stellate Cells into Myofibroblasts

RNA Binding Proteins Control Transdifferentiation of Hepatic Stellate Cells into Myofibroblasts

IMP3, a Promising Prognostic Marker in Clear Cell Renal Cell Carcinoma

RNA-binding protein IGF2BP3 targeting of oncogenic transcripts promotes hematopoietic progenitor proliferation

Contact Info

Product

Resources

About