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Circular RNA circKIF4A Sponges miR-375/1231 to Promote Bladder Cancer Progression by Upregulating NOTCH2 Expression
Ying-Rui Shi1,2, Zheng Wu2, Kun Xiong1
1Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
Abstract:
Circular RNAs (circRNAs) have been found to be important mediators of many biological processes in the growth and metastasis of various cancers. However, the potential roles of most circRNAs in the progression of bladder cancer remain unclear. In this research, we investigate the role of circKIF4A (hsa_circ_0007255) in the development and progression of bladder cancer. Detected by qRT-PCR analysis, circKIF4A was significantly upregulated in bladder cancer tissues and cell lines. We conducted CCK-8, colony-formation, transwell and mouse xenograft assays to explore the function of circKIF4A in bladder cancer. Functionally, knockdown of circKIF4A inhibited the proliferation and colony-formation ability of bladder cancer cells. Migration and metastatic ability were dramatically decreased after transfection with small interfering RNA targeting circKIF4A in both in vitro and in vivo assays. Mechanically, luciferase reporter assays and RNA immunoprecipitation assays were carried out to elucidate the underlying molecular mechanism of circKIF4A. The results revealed that circKIF4A sponges miR-375/1231 to promote bladder cancer progression by upregulating NOTCH2. Generally, our research unveils the essential role of circKIF4A-miR-375/1231-NOTCH2 axis in bladder cancer progression possibly via the competing endogenous RNA mechanism.
Insights
Circular RNAs (circRNAs) promote bladder cancer growth and metastasis. This study identifies circKIF4A as a key player, highlighting the circKIF4A-miR-375/1231-NOTCH2 axis in cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in cancer development and metastasis.
- The specific roles of most circRNAs in bladder cancer progression are not well understood.
Purpose of the Study:
- To investigate the function and mechanism of circKIF4A (hsa_circ_0007255) in bladder cancer development and progression.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) for circKIF4A expression detection.
- Cell proliferation (CCK-8, colony-formation), migration, and invasion (Transwell) assays.
- In vivo mouse xenograft models and molecular mechanism studies (luciferase reporter, RNA immunoprecipitation assays).
Main Results:
- CircKIF4A was significantly upregulated in bladder cancer tissues and cell lines.
- Knockdown of circKIF4A inhibited bladder cancer cell proliferation, colony formation, migration, and metastasis in vitro and in vivo.
- CircKIF4A acts as a sponge for miR-375/1231, upregulating NOTCH2 and promoting bladder cancer progression via the competing endogenous RNA (ceRNA) mechanism.
Conclusions:
- CircKIF4A plays a critical role in promoting bladder cancer progression.
- The circKIF4A-miR-375/1231-NOTCH2 axis is a potential therapeutic target for bladder cancer treatment.
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