IGF2BP3 promotes cell metastasis and is associated with poor patient survival in nasopharyngeal carcinoma

Xu, Yun; Guo, Zhoubo; Peng, Hewei; Guo, Lei; Wang, Ping

doi:10.1111/jcmm.17093

Cited by 18 publications

(19 citation statements)

References 33 publications

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“…Previous studies reported that IGF2BP3 is critical for tumorigenesis and associated with poor patient survival. 41,42 Here, we noticed that IGF2BP3 affected cell-matrix adhesion through disturbing alternative splicing profiles in LUAD. Thus, IGF2BP3 is an attractive therapeutic target as demonstrated in this study and other researches.…”

Section: Discussionmentioning

confidence: 91%

Multi-omics analysis reveals RNA splicing alterations and their biological and clinical implications in lung adenocarcinoma

Wang

et al. 2022

Sig Transduct Target Ther

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Alternative RNA splicing is one of the most important mechanisms of posttranscriptional gene regulation, which contributes to protein diversity in eukaryotes. It is well known that RNA splicing dysregulation is a critical mechanism in tumor pathogenesis and the rationale for the promising splice-switching therapeutics for cancer treatment. Although we have a comprehensive understanding of DNA mutations, abnormal gene expression profiles, epigenomics, and proteomics in lung adenocarcinoma (LUAD), little is known about its aberrant alternative splicing profiles. Here, based on the multi-omics data generated from over 1000 samples, we systematically studied the RNA splicing alterations in LUAD and revealed their biological and clinical implications. We identified 3688 aberrant alternative splicing events (AASEs) in LUAD, most of which were alternative promoter and exon skip. The specific regulatory roles of RNA binding proteins, somatic mutations, and DNA methylations on AASEs were comprehensively interrogated. We dissected the functional implications of AASEs and concluded that AASEs mainly affected biological processes related to tumor proliferation and metastasis. We also found that one subtype of LUAD with a particular AASEs pattern was immunogenic and had a better prognosis and response rate to immunotherapy. These findings revealed novel events related to tumorigenesis and tumor immune microenvironment and laid the foundation for the development of splice-switching therapies for LUAD.

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Section: Discussionmentioning

confidence: 91%

Multi-omics analysis reveals RNA splicing alterations and their biological and clinical implications in lung adenocarcinoma

Wang

et al. 2022

Sig Transduct Target Ther

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“…According to the above results, to search the further regulatory mechanism of IGF2BP3, we deeply studied the potential related signaling pathways of IGF2BP3 and treated with their inhibitors-AKT pathway (AKT-I), P13K pathway (PI3K-I), mTOR pathway (mTOR-I), p38MAPK pathway (p38MAPK-I) and IGF pathway (IGF-I), which have been reported before [34–36]. The results demonstrated that the expressions of IGF2BP3 have no significant difference among all the treatments expect to co-treat with overexpression of IGF2BP3, which revealed that IGF2BP3 expression wasn’t impacted by inhibiting these pathways (Fig.…”

Section: Resultsmentioning

confidence: 97%

“…Thus, our results demonstrated that overexpression of IGF2BP3 could upregulate the expression of CYP19A1 and StAR and facilitate the levels of E2 and P4 in follicular GCs, which was consistent with those results of overexpression of circEML1 and inhibition of gga-miR-449a. Some researches have reported that IGF2BP3 could act as an upstream regulator of AKT/mTOR signaling in hepatocellular carcinoma and promote nasopharyngeal carcinoma migration and invasion by activating the AKT/mTOR signaling pathway [36,67]. In addition, IGF2BP3 has also been revealed to evoke p53, p38/MAPK signal transduction events, and involved in the occurrence and development of acute myeloid leukemia (AML) [68].…”

Section: Discussionmentioning

confidence: 99%

CircEML1 facilitates the steroid synthesis in follicular granulosa cells of chicken through sponging gga-miR-449a to release IGF2BP3 expression

et al. 2022

Preprint

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Non-coding RNAs (ncRNAs) induced competing endogenous RNAs (ceRNA) play crucial roles in various biological process by regulating target gene expression. However, the studies of ceRNA networks in the regulation of ovarian ovulation process of chicken remains deficient compared to that in mammals. In the present study, it was revealed that circEML1 was differential expressed in hen’s ovarian tissue at different ages (15W, 20W, 30W and 68W) and identified as a loop structure from EML1 pre-mRNA, which promoted the expressions of CYP19A1 and StAR and the production of E2 and P4 in follicular granulosa cells (GCs) using qRT-PCR and ELISA. Furthermore, circEML1 was proved to serve as a sponge of gga-miR-449a to participate in the steroidogenesis using the dual luciferase reporter, RNA FISH assays, qRT-PCR and ELISA assays. In addition, we evaluated several potential target genes of gga-miR-449a and found that IGF2BP3 was targeted by gga-miR-449a and promoted steroidogenesis and E2/P4 secretions in GCs, which may act the regulatory role via mTOR/p38MAPK pathways. Meanwhile, we implemented a rescue experiment and demonstrated that gga-miR-449a reversed the promoting role of circEML1 on IGF2BP3 expression and steroidogenesis. Eventually, this study suggested that circEML1/gga-miR-449a/IGF2BP3 axis exerted an important role in the regulation of steroidogenesis and steroid hormones’ production possibly through mTOR/p38MAPK pathways in follicular GCs of chicken and may contribute a better understanding of ceRNA network in the modulatory mechanism of hen’s ovarian development and ovulation cycle.

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“…These results suggested that future studies should focus more on the expression of gene subtypes or different transcripts rather than the overall expression level of genes. As a member of the IGF2BPs family, a series of studies have shown that IGF2BP3 is associated with the proliferation and metastasis of colon cancer [ 41 ], bladder cancer [ 42 ], gastric cancer [ 43 ], and other malignant tumours [ 44 , 45 ]. In addition, IGF2BP3 can also participate in the regulation of mRNA stability and translation through the recognition of m 6 A sites, such as MYC, CDK6, or Cyclin D1 [ 41 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of prognosis-related alternative splicing events in ovarian cancer

Wang¹,

Wang

Zhang

et al. 2022

RNA Biology

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Ovarian cancer (OV) is characterized by high incidence and poor prognosis. Increasing evidence indicates that aberrant alternative splicing (AS) events are associated with the pathogenesis of cancer. We examined prognosis-related alternative splicing events and constructed a clinically applicable model to predict patients’ outcomes. Public database including The Cancer Genome Atlas (TCGA), TCGA SpliceSeq, and the Genomics of Drug Sensitivity in Cancer databases were used to detect the AS expression, immune cell infiltration and IC50. The prognosis-related AS model was constructed and validated by using Cox regression, LASSO regression, C-index, calibration plots, and ROC curves. A total of eight AS events (including FLT3LG|50942|AP) were selected to establish the prognosis-related AS model. Compared with high-risk group, low-risk group had a better outcome ( P = 1.794e-06), was more sensitive to paclitaxel ( P = 0.022), and higher proportions of plasma cells. We explored the upstream regulatory mechanisms of prognosis-related AS and found that two splicing factor and 156 tag single nucleotide polymorphisms may be involved in the regulation of prognosis-related AS. In order to assess patient prognosis more comprehensively, we constructed a clinically applicable model combining risk score and clinicopathological features, and the 1 -, and 3-year AUCs of the clinically applicable model were 0.812, and 0.726, which were 7.5% and 3.3% higher than that of the risk score. We constructed a prognostic signature for OV patients and comprehensively analysed the regulatory characteristics of the prognostic AS events in OV.

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IGF2BP3 promotes cell metastasis and is associated with poor patient survival in nasopharyngeal carcinoma

Cited by 18 publications

References 33 publications

Multi-omics analysis reveals RNA splicing alterations and their biological and clinical implications in lung adenocarcinoma

Multi-omics analysis reveals RNA splicing alterations and their biological and clinical implications in lung adenocarcinoma

CircEML1 facilitates the steroid synthesis in follicular granulosa cells of chicken through sponging gga-miR-449a to release IGF2BP3 expression

Comprehensive analysis of prognosis-related alternative splicing events in ovarian cancer

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