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The novel circular RNA circ-PGAP3 retards cervical cancer growth by regulating the miR-769-5p/p53 axis
Tian Jun1, Wang Chen2, Cheng Hailing1
1Department of Gynecology, HuaiHe Hosipital of Henan University, Kaifeng, 475001, Henan, China.
Abstract:
Cervical cancer (CC) is still an intractable disease that seriously affects women's health. Elucidating its pathogenesis will bring new targets for clinical treatment. Circular RNA (circRNA) is an endogenous RNA that has recently been reported to be closely related to cancer progression and development. In the current study, by performing in silico analysis and qRT-PCR assay, we found a circRNA derived from PGAP3, referred as circ-PGAP3 (hsa_circ_0106800, chr17:37843549-37844086), which was significantly downregulated in CC tissues. Low circ-PGAP3 was closely linked to poor prognosis. And overexpression of circ-PGAP3 significantly reduced CC cell proliferation in vitro and tumor growth in vivo. In terms of mechanism, circ-PGAP3 was transcriptionally elevated by p53, a well-recognized tumor suppressor, and circ-PGAP3 was located in the cytoplasm where sponged miR-769-5p to increase the levels of p53 and its downstream targets. Importantly, the regulatory feedback loop of circ-PGAP3/p53 was also confirmed in vivo. Overall, our data clearly expounded the tumor-inhibiting role of circ-PGAP3 in CC, circ-PGAP3 repressed CC tumorigenesis via regulating the miR-769-5p/p53 axis. Therefore, restoration of circ-PGAP3 may be a promising therapeutic target for this thorny disease.
Insights
Circular RNA circ-PGAP3 is downregulated in cervical cancer (CC) and inhibits tumor growth. Restoring circ-PGAP3 may offer a new therapeutic strategy for CC by regulating the miR-769-5p/p53 axis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cervical cancer (CC) remains a significant health challenge for women globally.
- Understanding CC pathogenesis is crucial for developing effective clinical treatments.
- Circular RNAs (circRNAs) are emerging as key players in cancer development and progression.
Purpose of the Study:
- To identify and characterize novel circRNAs involved in cervical cancer.
- To elucidate the functional role and underlying mechanism of circ-PGAP3 in CC.
- To explore the potential of circ-PGAP3 as a therapeutic target for cervical cancer.
Main Methods:
- In silico analysis and quantitative real-time PCR (qRT-PCR) to identify and quantify circ-PGAP3 expression in CC tissues.
- In vitro cell proliferation assays and in vivo tumor growth experiments to assess the functional impact of circ-PGAP3.
- Mechanism studies involving p53, miR-769-5p, and downstream targets to elucidate the regulatory pathway.
Main Results:
- A novel circRNA, circ-PGAP3 (hsa_circ_0106800), was found to be significantly downregulated in CC tissues.
- Low circ-PGAP3 expression correlated with poor patient prognosis.
- Overexpression of circ-PGAP3 suppressed CC cell proliferation in vitro and tumor growth in vivo.
- circ-PGAP3 acts as a tumor suppressor by sponging miR-769-5p, thereby increasing p53 levels and inhibiting CC tumorigenesis.
- A regulatory feedback loop between circ-PGAP3 and p53 was confirmed in vivo.
Conclusions:
- circ-PGAP3 plays a critical tumor-inhibiting role in cervical cancer.
- The circ-PGAP3/miR-769-5p/p53 axis represents a novel regulatory pathway in CC pathogenesis.
- Restoration of circ-PGAP3 holds promise as a potential therapeutic strategy for cervical cancer.
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