RNA-binding protein RNPC1 acts as an oncogene in gastric cancer by stabilizing Aurora kinase B mRNA

RNA-binding proteins have been associated with cancer development. The overexpression of a well-known RNA-binding protein, insulin-like growth factor 2 messenger RNA–binding protein 3, has been identified as an indicator of poor prognosis in patients with various types of cancer. Although gastric cancer is a relatively frequent and potentially fatal malignancy, the mechanism by which insulin-like growth factor 2 messenger RNA–binding protein 3 regulates the development of this cancer remains unclear. This study aimed to investigate the role and regulatory mechanism of insulin-like growth factor 2 messenger RNA–binding protein 3 in gastric cancer. An analysis of IGF2BP3 expression patterns reported in 4 public gastric cancer–related microarray data sets from the Gene Expression Omnibus and The Cancer Genome Atlas-Stomach Adenocarcinoma revealed strong expression of this gene in gastric cancer tissues. Insulin-like growth factor 2 messenger RNA–binding protein 3 expression in gastric cancer was further confirmed via quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively, in an in-house gastric cancer cohort (n = 30), and the association of insulin-like growth factor 2 messenger RNA–binding protein 3 expression with clinical parameters and prognosis was analyzed. Notably, stronger IGF2BP3 expression significantly correlated with poor prognosis, and significant changes in insulin-like growth factor 2 messenger RNA–binding protein 3 expression were only confirmed in patients with advanced-stage gastric cancer in an independent cohort. The effects of insulin-like growth factor 2 messenger RNA–binding protein 3 on cell proliferation were confirmed through in vitro experiments involving the HGC-27 gastric cancer cell line. MicroR-125a-5p, a candidate microRNA that target on insulin-like growth factor 2 messenger RNA–binding protein 3, decreased in advanced-stage gastric cancer. Upregulation of microR-125a-5p inhibited insulin-like growth factor 2 messenger RNA–binding protein 3, and dual-luciferase report assay indicated that microR-125a-5p inhibited the translation of IGF2BP3 by directly targeting the 3′ untranslated region. These results indicate that the microR-125a-5p/insulin-like growth factor 2 messenger RNA–binding protein 3 axis contributes to the oncogenesis of advanced gastric cancer.

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Abstract 5162: Id1 is an oncogenic target of RNA binding protein HuR in gastric cancer

10.1158/1538-7445.am2016-5162 ◽

2016 ◽

Author(s):

Shuang Han ◽

Xiaoqing Wu ◽

Yuxiao Guo ◽

Jing Zhang ◽

Xuan Gu ◽

...

Keyword(s):

Gastric Cancer ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein

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A Novel RNA-Binding Protein-Based Nomogram for Predicting Survival of Patients with Gastric Cancer

Medical Science Monitor ◽

10.12659/msm.928195 ◽

2020 ◽

Vol 27 ◽

Author(s):

Maoshu Zhu ◽

Jiading Cai ◽

Yulong Wu ◽

Xinhong Wu ◽

Lianghua Feng ◽

...

Keyword(s):

Gastric Cancer ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein

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A Novel RNA-Binding Protein Signature to Predict Clinical Outcomes and Guide Clinical Therapy in Gastric Cancer

Frontiers in Medicine ◽

10.3389/fmed.2021.670141 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhigang Qiu ◽

Haitao Jiang ◽

Kun Ju ◽

Xichun Liu

Keyword(s):

Gastric Cancer ◽

High Risk ◽

Clinical Outcomes ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Low Risk ◽

Survival Prediction ◽

Clinical Therapy ◽

Tumor Purity

Objective: This study aimed to develop an RNA-binding protein (RBP)-based signature for risk stratification and guiding clinical therapy in gastric cancer.Methods: Based on survival-related RBPs, an RBP-based signature was established by LASSO regression analysis in TCGA dataset. Kaplan–Meier curves were drawn between high- and low-risk groups. The predictive efficacy of this signature was assessed via ROCs at 1-, 3-, and 5-year survival. Its generalizability was verified in an external dataset. Following adjustment with other clinicopathological characteristics, the independency of survival prediction was evaluated via multivariate Cox regression and subgroup analyses. GSEA was utilized in identifying activated pathways in two groups. Stromal score, immune score, tumor purity, and infiltration levels of 22 immune cells were determined in each sample via the ESTIMATE and CIBERSORT algorithms. The sensitivity to chemotherapy drugs was assessed through the GDSC database.Results: Data showed that patients with high risk exhibited unfavorable clinical outcomes than those with low risk. This signature possessed good performance in predicting 1-, 3-, and 5-year survival and can be independently predictive of patients' survival. Calcium, ECM receptor interaction, and focal adhesion were highly enriched in high-risk samples. High-risk samples presented increased stromal and immune scores and reduced tumor purity. Moreover, this signature presented close relationships with immune infiltrations. Low-risk specimens were more sensitive to sorafenib, gefitinib, vinorelbine, and gemcitabine than high-risk specimens.Conclusion: This RBP-based signature may be a promising tool for predicting clinical outcomes and guiding clinical therapy in gastric cancer.

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RNA binding protein Lin28B confers gastric cancer cells stemness via directly binding to NRP-1

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2018.05.064 ◽

2018 ◽

Vol 104 ◽

pp. 383-389 ◽

Cited By ~ 6

Author(s):

Xiaocong Wang ◽

Huihua Hu ◽

Hebo Liu

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Gastric Cancer Cells

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RNA Binding Protein RNPC1 Promotes Gastric Cancer Progression via Stabilizing the Aurora Kinase B mRNA

10.21203/rs.3.rs-148988/v1 ◽

2021 ◽

Author(s):

Chunmei Ji ◽

Xu Zhang ◽

Wentong Fang ◽

Ling Meng ◽

Xiaolong Wei ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Mrna Stability ◽

Rna Binding ◽

Aurora Kinase ◽

Luciferase Reporter ◽

Gastric Cancer Cells ◽

Aurora Kinase B ◽

Potential Biomarker

Abstract BackgroundRNPC1, was reported to act as a tumor suppressor by binding and regulating the expression of the target genes in various cancers. However, the role of RNPC1 on the gastric cancer and the underly mechanisms were still unclear.MethodsGastric cancer cells were stably transfected with lentivirus. Proliferation, migration, invasion, cell cycle in vitro as well as tumorigenesis in vivo were performed to assess the role of RNPC1. Quantitative real-time PCR, western blot and immunohistochemistry were used to detect the relation between RNPC1 and Aurora kinase B (AURKB). RNA immunoprecipitation(RIP), RNA electrophoretic mobility shift assay (REMSA), dual-luciferase reporter assay were employed to identify the direct binding sites of RNPC1 with AURKB mRNA. CCK-8 assay conducted to confirm the function of AURKB in RNPC1-induced growth promotion. ResultsHigh RNPC1 expression was found in gastric cancer tissues and cell lines, associated with high TNM stage. RNPC1 overexpression could significantly promote the proliferation, migration, invasion of gastric cancer cells. Knockdown of RNPC1 could impede gastric cancer tumorigenesis in nude mice. AURKB expression was positively related with RNPC1. RNPC1 binded to the 3'-untranslated region (3'-UTR) of AURKB directly and enhanced AURKB mRNA stability. AURKB could reversed the proliferation induced by RNPC1 in gastric cancer cells. RNPC1 resulted in mitotic defects, aneuploidy and chromosomal instability in gastric cancer cells, as AURKB did. ConclusionRNPC1 acted as an oncogene in gastric cancer by influencing cell mitosis by regulating AURKB mRNA stability, which may provide a potential biomarker and therapeutic target for gastric cancer.

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