IGF2BP3 facilitates cell proliferation and tumorigenesis via modulation of JAK/STAT signalling pathway in human bladder cancer

Huang, Wei; Li, Yuanyuan; Zhang, Cheng; Zha, Huihai; Zhou, Xiaocheng; Fu, Bin; Guo, Ju; Wang, Gongxian

doi:10.1111/jcmm.16003

Cited by 85 publications

(53 citation statements)

References 36 publications

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“… 3 IGF2BP3 was found to be involved in controlling cell invasion and metastasis, proliferation, chemoresistance and tumorigenesis. 4 , 5 , 6 , 7 , 8 , 9 Moreover, IGF2BP3 was also implicated in the regulation of cancer stemness, metabolism and immunity. 10 , 11 , 12 , 13 Accumulating evidence indicates that IGF2BP3 plays a tumour‐promoting role in human cancers.…”

Section: Introductionmentioning

confidence: 99%

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

Guo

Peng

et al. 2021

J Cellular Molecular Medi

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Nasopharyngeal carcinoma (NPC) has obvious geographical distribution characteristics and is commonly diagnosed in certain regions of east and southeast Asia, such as China. 1 In particular, NPC mainly occurs in the southern provinces of China and ranks first among head and neck malignant tumours in Fujian. Treatment with induction chemotherapy plus concurrent chemoradiotherapy has improved the 5-year overall survival (OS) of patients with stage III-IVB NPC to 86%, while 22% of the patients develop locoregional or distant failures. 2 Therefore, it is necessary to clarify the underlying mechanisms of NPC metastasis and identify novel prognostic factors and targets for NPC.Insulin-like growth factor 2 mRNAs binding protein 3 (IGF2BP3) is a highly conserved member of the insulin-like growth factor 2 mRNAs binding protein family. IGF2BP3 functions as a post-transcriptional

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Section: Introductionmentioning

confidence: 99%

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

Guo

Peng

et al. 2021

J Cellular Molecular Medi

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“…Therefore, overexpression of TNFAIP8L3, caused by hypomethylation, may contribute to BLCA progression or resistance to therapies. MAPK signaling and JAK-STAT signaling pathways have been shown to have vital roles in BLCA progression and might be connected with TNFAIP8L3 activation ( Huang et al, 2020 ; Lei et al, 2020 ), but the mechanisms connecting TNFAIP8L3 and these two pathways remain unclear. Further studies are required.…”

Section: Discussionmentioning

confidence: 99%

A Novel CpG Methylation Risk Indicator for Predicting Prognosis in Bladder Cancer

Guo

Yin

Dai

et al. 2021

Front. Cell Dev. Biol.

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PurposeBladder cancer (BLCA) is one of the most common cancers worldwide. In a large proportion of BLCA patients, disease recurs and/or progress after resection, which remains a major clinical issue in BLCA management. Therefore, it is vital to identify prognostic biomarkers for treatment stratification. We investigated the efficiency of CpG methylation for the potential to be a prognostic biomarker for patients with BLCA.Patients and MethodsOverall, 357 BLCA patients from The Cancer Genome Atlas (TCGA) were randomly separated into the training and internal validation cohorts. Least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) were used to select candidate CpGs and build the methylation risk score model, which was validated for its prognostic value in the validation cohort by Kaplan–Meier analysis. Hazard curves were generated to reveal the risk nodes throughout the follow-up. Gene Set Enrichment Analysis (GSEA) was used to reveal the potential biological pathways associated with the methylation model. Quantitative real-time polymerase chain reaction (PCR) and western blotting were performed to verify the expression level of the methylated genes.ResultsAfter incorporating the CpGs obtained by the two algorithms, CpG methylation of eight genes corresponding to TNFAIP8L3, KRTDAP, APC, ZC3H3, COL9A2, SLCO4A1, POU3F3, and ADARB2 were prominent candidate predictors in establishing a methylation risk score for BLCA (MRSB), which was used to divide the patients into high- and low-risk progression groups (p < 0.001). The effectiveness of the MRSB was validated in the internal cohort (p < 0.001). In the MRSB high-risk group, the hazard curve exhibited an initial wide, high peak within 10 months after treatment, whereas some gentle peaks around 2 years were noted. Furthermore, a nomogram comprising MRSB, age, sex, and tumor clinical stage was developed to predict the individual progression risk, and it performed well. Survival analysis implicated the effectiveness of MRSB, which remains significant in all the subgroup analysis based on the clinical features. A functional analysis of MRSB and the corresponding genes revealed potential pathways affecting tumor progression. Validation of quantitative real-time PCR and western blotting revealed that TNFAIP8L3 was upregulated in the BLCA tissues.ConclusionWe developed the MRSB, an eight-gene-based methylation signature, which has great potential to be used to predict the post-surgery progression risk of BLCA.

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“…IGF2BP3 is a member of the IGF2 mRNA binding protein family—also known as the m 6 A binding protein—which exerts its biological functions in various human cancers [ 35 ]. IGF2BP3 functions as an oncofoetal factor in multiple tumour types, facilitating tumorigenesis by regulating the cell cycle, proliferation, and angiogenesis [ 36 , 37 ]. In the previous studies, IGF2BP3 was considered a poor prognostic factor for NSCLC, prostate cancer, and endocrine system tumours [ 38 – 40 ].…”

Section: Discussionmentioning

confidence: 99%

m6A regulator expression profile predicts the prognosis, benefit of adjuvant chemotherapy, and response to anti-PD-1 immunotherapy in patients with small-cell lung cancer

Zhang

Luo

et al. 2021

BMC Med

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Background Small cell lung cancer (SCLC) is lethal and possesses limited therapeutic options. Platinum-based chemotherapy—with or without immune checkpoint inhibitors (anti-PDs)—is the current first-line therapy for SCLCs; however, its associated outcomes are heterogeneous. N6-methyladenosine (m6A) is a novel and decisive factor in tumour progression, chemotherapy resistance, and immunotherapy response. However, m6A modification in SCLC remains poorly understood. Methods We systematically explored the molecular features and clinical significance of m6A regulators in SCLC. We then constructed an m6A regulator-based prognostic signature (m6A score) based on our examination of 256 cases with limited-stage SCLC (LS-SCLC) from three different cohorts—including an independent cohort that contained 150 cases with qPCR data. We additionally evaluated the relationships between the m6A score and adjuvant chemotherapy (ACT) benefits and the patients’ responses to anti-PD-1 treatment. Immunohistochemical (IHC) staining and the HALO digital pathological platform were used to calculate CD8+ T cell density. Results We observed abnormal somatic mutations and expressions of m6A regulators. Using the LASSO Cox model, a five-regulator-based (G3BP1, METTL5, ALKBH5, IGF2BP3, and RBM15B) m6A score was generated from the significant regulators to classify patients into high- and low-score groups. In the training cohort, patients with high scores had shorter overall survival (HR, 5.19; 2.75–9.77; P < 0.001). The prognostic accuracy of the m6A score was well validated in two independent cohorts (HR 4.6, P = 0.006 and HR 3.07, P < 0.001). Time-dependent ROC and C-index analyses found the m6A score to possess superior predictive power than other clinicopathological parameters. A multicentre multivariate analysis revealed the m6A score to be an independent prognostic indicator. Additionally, patients with low scores received a greater survival benefit from ACT, exhibited more CD8+ T cell infiltration, and were more responsive to cancer immunotherapy. Conclusions Our results, for the first time, affirm the significance of m6A regulators in LS-SCLC. Our multicentre analysis found that the m6A score was a reliable prognostic tool for guiding chemotherapy and immunotherapy selections for patients with SCLC.

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IGF2BP3 facilitates cell proliferation and tumorigenesis via modulation of JAK/STAT signalling pathway in human bladder cancer

Cited by 85 publications

References 36 publications

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

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

A Novel CpG Methylation Risk Indicator for Predicting Prognosis in Bladder Cancer

m6A regulator expression profile predicts the prognosis, benefit of adjuvant chemotherapy, and response to anti-PD-1 immunotherapy in patients with small-cell lung cancer

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