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Circular RNA DHX33 promotes malignant behavior in ccRCC by targeting miR-489-3p/MEK1 axis
Jie Wang1,2, Jian-Qiu Zhang1,2, Xiao-Lei Zhao3
1Department of Urology, Ninghai First Hospital, Zhejiang 315600, China.
Abstract:
Mounting evidence indicates that circular RNAs modulate the initiation of clear cell renal cell carcinoma (ccRCC). However, their specific roles in the malignancy of ccRCC is understudied. Here, we present a novel circular RNA, circDHX33, that is up-regulated in ccRCC cell lines and tissues. Upregulated circDHX33 in ccRCC patients significantly correlates with advanced TNM stage and metastasis. Suppressing circDHX33 expression inhibits the proliferation and invasion of cultured cells, and suppresses tumor growth in vivo. Mechanistically, we show that circDHX33 promotes ccRCC progression by sponging miR-489-3p and modulating MEK1 expression. In conclusion, our findings suggest that circDHX33 plays a role in promoting ccRCC via the miR-489-3p/MEK1 axis and may serve as a novel therapeutic target for the treatment of ccRCC patients.
Insights
A novel circular RNA, circDHX33, promotes clear cell renal cell carcinoma (ccRCC) progression by regulating the miR-489-3p/MEK1 pathway. Targeting circDHX33 may offer a new therapeutic strategy for ccRCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer development.
- The specific involvement of circRNAs in the progression of clear cell renal cell carcinoma (ccRCC) remains largely unexplored.
Purpose of the Study:
- To investigate the function and mechanism of a novel circRNA, circDHX33, in ccRCC.
- To determine if circDHX33 could serve as a potential therapeutic target for ccRCC.
Main Methods:
- Quantitative real-time PCR to measure circDHX33 expression in ccRCC cell lines and tissues.
- Cell proliferation and invasion assays.
- In vivo tumor growth experiments.
- Mechanistic studies involving microRNA (miRNA) sponging and gene expression analysis.
Main Results:
- circDHX33 was found to be upregulated in ccRCC cell lines and patient tissues.
- Higher circDHX33 levels correlated with advanced TNM stage and metastasis in ccRCC patients.
- Inhibition of circDHX33 suppressed ccRCC cell proliferation, invasion, and tumor growth in vivo.
- circDHX33 was shown to promote ccRCC progression by sponging miR-489-3p and consequently modulating MEK1 expression.
Conclusions:
- circDHX33 acts as an oncogenic circRNA in ccRCC progression.
- The circDHX33/miR-489-3p/MEK1 axis is a key pathway driving ccRCC malignancy.
- circDHX33 represents a promising novel therapeutic target for ccRCC.
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