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RNA-binding protein IGF2BP2 suppresses metastasis of clear cell renal cell carcinoma by enhancing CKB mRNA stability
Junwu Ren1, Bo Huang2, Wei Li3
1College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China.
Abstract:
Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer, with a highly aggressive phenotype and poor prognosis. RNA binding proteins (RBPs) play crucial roles in post-transcriptional gene regulation and have been implicated in tumorigenesis. RBPs have the potential to become a new therapeutic target for ccRCC. In this study, we screened and validated that insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) as an RBP, was down-regulated in ccRCC tissues and cell lines. Functionally, we verified that IGF2BP2 significantly suppressed the migration and invasion ability of ccRCC in vitro and in vivo. Mechanistically, RIP-seq and actinomycin D experiments results showed that IGF2BP2 enhanced the expression of Creatine Kinase B (CKB) by binding to CKB mRNA and enhancing its mRNA stability. Thus, IGF2BP2 inhibited ccRCC metastasis through enhancing the expression of CKB. Taken together, these finding suggests that IGF2BP2 is a novel metastasis suppressor of ccRCC and may serve as a potential therapeutic target.
Insights
Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) suppresses clear cell renal cell carcinoma (ccRCC) metastasis. This RNA binding protein enhances Creatine Kinase B (CKB) expression, offering a potential therapeutic target for kidney cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Clear cell renal cell carcinoma (ccRCC) is an aggressive kidney cancer with poor prognosis.
- RNA binding proteins (RBPs) are critical in gene regulation and implicated in cancer development.
- RBPs represent potential therapeutic targets for ccRCC.
Purpose of the Study:
- To identify and validate novel RNA binding proteins (RBPs) as therapeutic targets for ccRCC.
- To investigate the role of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) in ccRCC progression.
- To elucidate the molecular mechanism by which IGF2BP2 affects ccRCC metastasis.
Main Methods:
- Screening and validation of RBPs in ccRCC tissues and cell lines.
- In vitro and in vivo functional assays to assess ccRCC cell migration and invasion.
- RIP-seq and actinomycin D experiments to determine mRNA targets and stability.
- Analysis of IGF2BP2 and Creatine Kinase B (CKB) expression levels.
Main Results:
- IGF2BP2 was found to be downregulated in ccRCC tissues and cell lines.
- IGF2BP2 significantly suppressed ccRCC cell migration and invasion both in vitro and in vivo.
- IGF2BP2 enhances Creatine Kinase B (CKB) expression by increasing CKB mRNA stability.
- RIP-seq identified CKB mRNA as a target of IGF2BP2.
Conclusions:
- IGF2BP2 acts as a metastasis suppressor in ccRCC.
- IGF2BP2 inhibits ccRCC metastasis by enhancing CKB expression.
- IGF2BP2 is a potential therapeutic target for ccRCC treatment.
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