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Published on: August 9, 2024
Targeting Circ-OCAC suppress oral squamous cell carcinoma progression
Bowen Li1,2,3, Yuxun Ding1,4, Chuying Huo5
1Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
Objectives:
Circular RNAs (circRNAs), with their multilevel and versatile regulation, have emerged as promising targets for treating complex and heterogeneous malignancies such as oral squamous cell carcinoma (OSCC). It is crucial to explore the function of key circRNAs and elucidate the underlying mechanisms to establish an effective in vivo delivery system to better utilize circRNAs as cancer treatment strategies.
Materials And Methods:
circRNA (circ-OCAC) was identified as significantly downregulated in tumor samples compared to paracancerous tissues by RNA-seq analysis of eight pairs of OSCC tissues. Functional experiments of circ-OCAC were performed both in vitro and in vivo. The interactions between circ-OCAC and miR-411-5p were clarified by RNA pull down and RNA immunoprecipitation (RIP) assays.
Results:
We observed that circ-OCAC inhibits OSCC growth and metastasis by blocking the PI3K/Akt signaling pathway. To translate this observation in vivo, a pH-responsive nanoparticle (pNP) was developed to target circ-OCAC. Our results confirmed the advantages of the pNP-circ-OCAC system: high tumor enrichment capacity and good biosafety, which resulted in a significantly enhanced antitumor effect.
Conclusions:
This study demonstrated that targeting circ-OCAC serves as a promising potential therapeutic strategy for OSCC.
Insights
Targeting circular RNA (circRNA) circ-OCAC shows promise for treating oral squamous cell carcinoma (OSCC). A novel nanoparticle delivery system enhanced circ-OCAC
Area of Science:
- Oncology
- Molecular Biology
- Nanotechnology
Background:
- Circular RNAs (circRNAs) offer versatile regulatory functions and are potential therapeutic targets for complex cancers like oral squamous cell carcinoma (OSCC).
- Understanding the specific roles and delivery mechanisms of key circRNAs is essential for developing effective cancer treatments.
Purpose of the Study:
- To investigate the function of circRNA circ-OCAC in OSCC.
- To develop and evaluate an in vivo delivery system for circ-OCAC as a potential therapeutic strategy for OSCC.
Main Methods:
- RNA sequencing (RNA-seq) identified circ-OCAC as downregulated in OSCC tissues.
- In vitro and in vivo functional experiments assessed circ-OCAC's role.
- RNA pull down and RNA immunoprecipitation (RIP) assays elucidated interactions with miR-411-5p.
- A pH-responsive nanoparticle (pNP) system was developed for circ-OCAC delivery.
Main Results:
- Circ-OCAC inhibits OSCC growth and metastasis by suppressing the PI3K/Akt signaling pathway.
- The developed pNP-circ-OCAC system demonstrated high tumor enrichment and good biosafety.
- The pNP-circ-OCAC system significantly enhanced antitumor effects in vivo.
Conclusions:
- Circ-OCAC acts as a tumor suppressor in OSCC.
- Targeting circ-OCAC, particularly with the pNP delivery system, represents a promising therapeutic strategy for OSCC.
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