IGF2BP3 enhances the mRNA stability of E2F3 by interacting with LINC00958 to promote endometrial carcinoma progression

Wang, Cuicui; Kong, Fanfei; Ma, Jian; Jiang, Miao; Su, Peng; Yang, Hui; Li, Qing; Ma, Xiaoxin

doi:10.1038/s41420-022-01045-x

Cited by 20 publications

(17 citation statements)

References 47 publications

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“…In addition, STRIP2 upregulated IGF2BP3 transcription and protein levels, thus leading to formulate a STRIP2-IGF2BP3 positive loop in NSCLC progression. IGF2BP3 was considered as an m6A reader and contributed to tumor progression through mediating the stabilization of IGF2BP3 targets in an m6Adependent manner [35,46,47]. Our finding supports that STRIP2-IGF2BP3 axis stabilizes the TMBIM6 level in an m6A-dependent manner.…”

Section: Discussionsupporting

confidence: 82%

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

Zhang

Chen

et al. 2023

J Exp Clin Cancer Res

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Background Striatin interacting protein 2 (STRIP2) is a core component of the striatin-interacting phosphatase and kinase (STRIPAK) complexes, which is involved in tumor initiation and progression via the regulation of cell contractile and metastasis. However, the underlying molecular mechanisms of STRIP2 in non-small cell lung cancer (NSCLC) progression remain largely unknown. Methods The expressions of STRIP2 and IGF2BP3 in human NSCLC specimens and NSCLC cell lines were detected using quantitative RT-PCR, western blotting, and immunohistochemistry (IHC) analyses. The roles and molecular mechanisms of STRIP2 in promoting NSCLC progression were investigated in vitro and in vivo. Results Here, we found that STRIP2 expression was significantly elevated in NSCLC tissues and high STRIP2 expression was associated with a poor prognosis. Knockdown of STRIP2 suppressed tumor growth and metastasis in vitro and in vivo, while STRIP2 overexpression obtained the opposite effect. Mechanistically, P300/CBP-mediated H3K27 acetylation activation in the promoter of STRIP2 induced STRIP2 transcription, which interacted with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and upregulated IGF2BP3 transcription. In addition, STRIP2-IGF2BP3 axis stimulated m6A modification of TMBIM6 mRNA and enhanced TMBIM6 stability. Consequently, TMBIM6 involved NSCLC cell proliferation, migration and invasion dependent on STRIP2 and IGF2BP3. In NSCLC patients, high co-expression of STRIP2, IGF2BP3 and TMBIM6 was associated with poor outcomes. Conclusions Our findings indicate that STRIP2 interacts with IGF2BP3 to regulate TMBIM6 mRNA stability in an m6A-dependent manner and may represent a potential prognostic biomarker and therapeutic target for NSCLC.

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Section: Discussionsupporting

confidence: 82%

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

Zhang

Chen

et al. 2023

J Exp Clin Cancer Res

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“…IGF2BP3 has been reported to be upregulated in many types of tumors, including pancreatic cancer, 33 lung adenocarcinoma, 34 triple‐negative breast cancer, 35 colorectal cancer, 36 hepatocellular carcinoma, 37 and gliomas, 38 suggesting that IGF2BP3 can serve as a novel cancer biomarker for early diagnosis and prognosis. Mechanically, highly expressed IGF2BP3 served a moderating role to promote the proliferation, migration, and glycolysis of endometrial, nasopharyngeal, and liver carcinomas by enhancing the stability of specific genes, such as E2F3, 39 KPNA2, 40 and pyruvate dehydrogenase kinase 4 (PDK4) 41 . In addition, IGF2BP3 regulated target genes in an m 6 A‐dependent manner, contributing to cancer progression, cell cycle, angiogenesis, and drug resistance in different types of malignancies, including laryngeal squamous cell carcinoma, 42 colon cancer, 43 colorectal cancer, 44 and triple‐negative breast cancer 45 .…”

Section: Discussionmentioning

confidence: 99%

U‐shaped association between serum IGF2BP3 and T2DM: A cross‐sectional study in Chinese population

Wang

Fan

et al. 2023

Journal of Diabetes

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Objective To clarify the expression of N6‐methyladenosine (m6A) modulators involved in the pathogenesis of type 2 diabetes mellitus (T2DM). We further explored the association of serum insulin‐like growth factor 2 mRNA‐binding proteins 3 (IGF2BP3) levels and odds of T2DM in a high‐risk population. Methods The gene expression data set GSE25724 was obtained from the Gene Expression Omnibus, and a cluster heatmap was generated by using the R package ComplexHeatmap. Differential expression analysis for 13 m6A RNA methylation regulators between nondiabetic controls and T2DM subjects was performed using an unpaired t test. A cross‐sectional design, including 393 subjects (131 patients with newly diagnosed T2DM, 131 age‐ and sex‐matched subjects with prediabetes, and 131 healthy controls), was carried out. The associations between serum IGF2BP3 concentrations and T2DM were modeled by restricted cubic spline and logistic regression models. Results Two upregulated (IGF2BP2 and IGF2BP3) and 5 downregulated (methyltransferase‐like 3 [METTL3], alkylation repair homolog protein 1 [ALKBH1], YTH domain family 2 [YTHDF2], YTHDF3, and heterogeneous nuclear ribonucleoprotein [HNRNPC]) m6A‐related genes were found in islet samples of T2DM patients. A U‐shaped association existed between serum IGF2BP3 levels and odds of T2DM according to cubic natural spline analysis models, after adjustment for body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyeride. Multivariate logistic regression showed that progressively higher odds of T2DM were observed when serum IGF2BP3 levels were below 0.62 ng/mL (odds ratio 3.03 [95% confidence interval 1.23–7.47]) in model 4. Conclusion Seven significantly altered m6A RNA methylation genes were identified in T2DM. There was a U‐shaped association between serum IGF2BP3 levels and odds of T2DM in the general Chinese adult population. This study provides important evidence for further examination of the role of m6A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment.

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“…It was shown by previous studies that IGF2BP3 or IGF2BP3/circRNA complex stabilizes mRNA (Wang et al 2022). Therefore, we next investigated if IGF2BP3/ circ_AFF4 stabilizes downstream targets.…”

Section: Circ_aff4 Interacts With Igf2bp3 and Stabilizes Fndc5 Mrnamentioning

confidence: 98%

CircRNA AFF4 induced by KDM1A promotes osteogenic differentiation through FNDC5/Irisin pathway

Liu

Chen

Zhong

et al. 2022

Mol Med

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Background Circular RNA (circ) AFF4 was documented to regulate osteogenesis but the underlying mechanism remains to be elucidated. The preliminary study showed that circ_AFF4 may promote osteogenesis via FNDC5/Irisin. Furthermore, the online prediction tool indicated the interaction of circ_AFF4, insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3), FNDC5 and lysine (K)-specific demethylase 1 A (KDM1A). Therefore, this study aims to elucidate the relationships of KDM1A, circ_AFF4, IGF2BP3 and FNDC5/Irisin during osteogenesis. Methods The alkaline phosphatase (ALP) activities and osteogenic-related factors were determined using ALP and alizarin red S (ARS) staining, real-time quantitative PCR(RT-qPCR) and western blot. Immunoprecipitation (RIP), pull-down assay and fluorescence in situ hybridization (FISH) were used to examine the interactions among circ_AFF4/IGF2BP3/FNDC5. A mouse in vivo model was utilized to further confirm the regulatory effect on bone formation. Results Circ_AFF4 and KDM1A expression levels were increased during osteoinduction of BM-MSCs. Knockdown of circ_AFF4 and KDM1A significantly suppressed BM-MSC osteogenesis. We also proved that KDM1A directly bound to circ_AFF4 and FNDC5 promoter and induced circ_AFF4 and FNDC5 expression. Furthermore, circ_AFF4 enhanced the stability of FNDC5 by generating a circ_AFF4, IGF2BP3 and FNDC5 RNA-protein complex, and thereby induced Irisin and osteogenesis. The in vitro data was confirmed with in vivo model. Conclusion These findings elucidate that KDM1A induces circ_AFF4, which promotes promote osteogenesis via IGF2BP3. This study indicates that circ_AFF4 may potentially represent a critical therapeutic target for the diseases.

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IGF2BP3 enhances the mRNA stability of E2F3 by interacting with LINC00958 to promote endometrial carcinoma progression

Cited by 20 publications

References 47 publications

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

U‐shaped association between serum IGF2BP3 and T2DM: A cross‐sectional study in Chinese population

CircRNA AFF4 induced by KDM1A promotes osteogenic differentiation through FNDC5/Irisin pathway

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