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Updated: Aug 28, 2025
In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions
Published on: October 21, 2022
Magnetically responsive nanoplatform targeting circRNA circ_0058051 inhibits hepatocellular carcinoma progression
Song You1,2,3, Zijin Luo2, Niangmei Cheng2,4
1Department of Hepatobiliary Surgery, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, 350014, People's Republic of China.
Abstract:
Circular RNAs (circRNAs) are a class of highly stable and closed-loop noncoding RNA that are involved in the occurrence and development of hepatocellular carcinoma (HCC). However, little is known about the therapeutic role of circRNAs in HCC. We found that high circ_0058051 expression was negatively correlated with the prognosis of HCC patients. Circ_0058051 knockdown attenuated the proliferation and colony formation, meanwhile inhibited migration of HCC cells. Circ_0058051 may be used as a target for HCC gene therapy. We synthesized a novel small interfering RNA (siRNA) delivery system, PEG-PCL-PEI-C14-SPIONs (PPPCSs), based on superparamagnetic iron oxide nanoparticles (SPIONs). PPPCSs protected the siRNA of circ_0058051 from degradation in serum and effectively delivered siRNA into SMMC-7721 cells. Meanwhile, intravenous injection of the PPPCSs/siRNA complex could inhibit tumor growth in the subcutaneous tumor model. In addition, the nanocomposite is not toxic to the organs of nude mice. The above results show that PPPCSs/si-circ_0058051 complex may provide a novel and promising method of HCC treatment.
Insights
High expression of circ_0058051 correlates with poor prognosis in hepatocellular carcinoma (HCC). A novel nanoparticle system effectively delivered siRNA to inhibit HCC cell growth and tumor progression, offering a promising gene therapy approach for HCC.
Area of Science:
- Oncology
- Molecular Biology
- Nanotechnology
Background:
- Circular RNAs (circRNAs) are implicated in hepatocellular carcinoma (HCC) development, but their therapeutic potential remains largely unexplored.
- High expression of circ_0058051 is associated with unfavorable prognosis in HCC patients.
- circRNAs are stable, closed-loop noncoding RNA molecules with emerging roles in cancer.
Purpose of the Study:
- To investigate the therapeutic role of circ_0058051 in HCC.
- To develop and evaluate a novel nanoparticle-based delivery system for circRNA-targeted gene therapy in HCC.
Main Methods:
- Correlation analysis between circ_0058051 expression and HCC patient prognosis.
- Knockdown of circ_0058051 in HCC cells to assess effects on proliferation, colony formation, and migration.
- Synthesis and characterization of a novel siRNA delivery system (PPPCSs) based on superparamagnetic iron oxide nanoparticles (SPIONs).
- In vitro evaluation of PPPCSs/siRNA complex for serum stability and cellular uptake.
- In vivo assessment of PPPCSs/si-circ_0058051 complex efficacy in inhibiting tumor growth in a subcutaneous HCC mouse model.
- Evaluation of the nanocomposite's toxicity in nude mice.
Main Results:
- High circ_0058051 expression was negatively correlated with HCC patient survival.
- Knockdown of circ_0058051 significantly inhibited HCC cell proliferation, colony formation, and migration.
- The synthesized PPPCSs effectively protected circ_0058051 siRNA from degradation and facilitated its delivery into HCC cells.
- Intravenous administration of PPPCSs/si-circ_0058051 complex demonstrated significant inhibition of tumor growth in vivo.
- The nanocomposite exhibited no observable toxicity in the organs of nude mice.
Conclusions:
- Circ_0058051 serves as a potential therapeutic target for HCC.
- The novel PPPCSs nanoparticle system is a safe and effective vehicle for delivering siRNA against circ_0058051.
- The PPPCSs/si-circ_0058051 complex represents a promising novel strategy for HCC gene therapy.
