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Upregulated circ_0005576 facilitates cervical cancer progression via the miR-153/KIF20A axis
Hanyu Ma1, Tian Tian1, Xubin Liu1
1Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Abstract:
Circular RNAs (circRNAs) are a novel group of noncoding RNAs characterized by a covalently closed loop. An increasing evidence suggests that deregulated circRNAs exert their essential regulatory roles in oncogenesis. However, little is explored on the biological role of novel circRNAs in cervical cancer (CC) progression. In the present study, we analyzed two GSE microarrays to screen for CC-specific circRNAs and found two circRNAs both expressed in CC cells and tissues. Among them, circ_0005576 was significantly overexpressed in both CC tissues and cell lines. Furthermore, upregulated circ_0005576 was positively associated with advanced FIGO stage, lymph node metastasis, but was negatively related with overall survival of CC patients. Additionally, circ_0005576 knockdown induced a suppressed cell growth, colony formation and metastasis of HeLa and SiHa cells. Mechanistically, circ 0005576 was mainly located in the cytoplasm and served as a sponge of miR-153-3p to increase kinesin family member 20A (KIF20A) expression. Rescue assays further validated the effects of circ_0005576/miR-153-3p/KIF20A axis on CC proliferation, migration and invasion. In conclusion, our research reveals a novel circ_0005576/miR-153-3p/KIF20A axis promoting CC progression, which may suggest a new insight into the pathogenesis of CC.
Insights
Circular RNAs (circRNAs) promote cervical cancer (CC) progression. The novel circ_0005576 acts as a sponge for miR-153-3p, increasing KIF20A expression and driving CC cell growth and metastasis.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Circular RNAs (circRNAs) are emerging as critical regulators in oncogenesis.
- The specific roles of novel circRNAs in cervical cancer (CC) progression remain largely unexplored.
- Understanding these roles is crucial for identifying new therapeutic targets in CC.
Purpose of the Study:
- To identify novel circRNAs involved in cervical cancer (CC) progression.
- To elucidate the biological function and mechanism of circ_0005576 in CC.
- To investigate the potential of the circ_0005576/miR-153-3p/KIF20A axis as a therapeutic target.
Main Methods:
- Analysis of two Gene Expression Omnibus (GSE) microarrays to screen for CC-specific circRNAs.
- Quantitative real-time PCR (qRT-PCR) to assess circ_0005576 expression in CC tissues and cell lines.
- Cellular assays including knockdown, colony formation, migration, and invasion assays to evaluate circ_0005576 function.
- Mechanism investigation involving RNA immunoprecipitation (RIP) and dual-luciferase reporter assays to confirm the interaction between circ_0005576, miR-153-3p, and KIF20A.
Main Results:
- Two novel circRNAs were identified in CC, with circ_0005576 significantly overexpressed in CC tissues and cell lines.
- Elevated circ_0005576 levels correlated with advanced FIGO stage, lymph node metastasis, and poorer overall survival in CC patients.
- Knockdown of circ_0005576 suppressed CC cell proliferation, colony formation, and metastasis.
- Mechanistically, circ_0005576 acts as a molecular sponge for miR-153-3p, leading to increased expression of kinesin family member 20A (KIF20A).
- Rescue experiments confirmed the role of the circ_0005576/miR-153-3p/KIF20A axis in promoting CC progression.
Conclusions:
- A novel circ_0005576/miR-153-3p/KIF20A axis significantly promotes cervical cancer progression.
- Circ_0005576 may serve as a potential biomarker for CC diagnosis and prognosis.
- Targeting this axis offers a promising new therapeutic strategy for cervical cancer.
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