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Updated: Jul 1, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Silencing circLDLRAD3 Inhibits Lung Cancer Progression by Regulating the miR-497-5p/PFKP Axis
1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yantaxi Road, Xi'an, 710061, Shaanxi, China.
Purpose:
Lung cancer is one of the leading causes of death worldwide. Recent studies have shown that circular RNAs are dysregulated in a variety of cancers, but the mechanism in lung cancer is still indistinct. In our work, we explored the action mechanism of circLDLRAD3 in lung cancer.
Methods:
The abundance of circLDLRAD3, microRNA-497-5p (miR-497-5p) and platelet-type PFK (PFKP) was measured by real-time quantitative polymerase chain reaction (RT-qPCR) in lung cancer. Meanwhile, the level of PFKP was quantified by western blot. Cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) assay, transwell assay, wound healing assay, flow cytometry, western blot, immunohistochemical (IHC) assay and glycolysis metabolism analysis were performed for functional analyses. Furthermore, the interplay between miR-497-5p and circLDLRAD3 or FKPF was detected by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Eventually, the in vivo experiments were applied to measure the role of circLDLRAD3.
Result:
The levels of circLDLRAD3 and PFKP were increased. Silencing circLDLRAD3 inhibited cell viability, proliferation, migration, invasion and glycolysis metabolism and promoted cell apoptosis in lung cancer cells. In mechanism, circLDLRAD3 regulated PFKP level as a miR-497-5p sponge. MiR-497-5p suppressed the progression of lung cancer by inhibiting PFKP. In addition, circLDLRAD3 knockdown also inhibited tumor growth in vivo.
Conclusion:
CircLDLRAD3 promoted the development of lung cancer through increasing PFKP expression by regulating miR-497-5p, which also provided a potential targeted therapy for lung cancer treatment.
Insights
Circular RNA circLDLRAD3 promotes lung cancer by increasing PFKP via sponging miR-497-5p. Silencing circLDLRAD3 inhibits cancer progression and tumor growth, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Lung cancer is a leading global cause of mortality.
- Circular RNAs (circRNAs) are increasingly recognized as crucial regulators in various cancers.
- The specific role and mechanism of circRNAs, like circLDLRAD3, in lung cancer remain largely undefined.
Purpose of the Study:
- To elucidate the functional mechanism of circLDLRAD3 in lung cancer.
- To investigate the regulatory relationship between circLDLRAD3, microRNA-497-5p (miR-497-5p), and platelet-type PFK (PFKP) in lung cancer progression.
Main Methods:
- Quantification of circLDLRAD3, miR-497-5p, and PFKP expression using RT-qPCR and Western blot.
- In vitro functional assays including CCK-8, EdU, Transwell, wound healing, and flow cytometry.
- Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays to determine molecular interactions; in vivo tumor growth studies.
Main Results:
- circLDLRAD3 and PFKP levels were elevated in lung cancer tissues.
- circLDLRAD3 knockdown significantly suppressed cell viability, proliferation, migration, invasion, and glycolysis, while promoting apoptosis.
- circLDLRAD3 acts as a sponge for miR-497-5p, leading to increased PFKP expression; miR-497-5p inhibits lung cancer progression by targeting PFKP. circLDLRAD3 knockdown inhibited tumor growth in vivo.
Conclusions:
- circLDLRAD3 promotes lung cancer development by upregulating PFKP expression through sponging miR-497-5p.
- The circLDLRAD3/miR-497-5p/PFKP axis represents a novel regulatory pathway in lung cancer.
- circLDLRAD3 inhibition presents a potential targeted therapeutic strategy for lung cancer treatment.
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