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Hsa_circ_0008259 modulates miR-21-5p and PDCD4 expression to restrain osteosarcoma progression
Kai Guan1, Shizhang Liu2, Keke Duan2
1The Second Department of Orthopaedics, The First People's Hospital of Xianyang, Xianyang 712000, Shaanxi Province, China.
Background:
Osteosarcoma (OS) is one of the most common primary bone tumors in children and adolescents. However, the molecular mechanism of OS tumorigenesis is still little known. Circular RNA (circRNA) is a key player in the progression of many cancers. This study is performed to decipher the role and mechanism of circ_0008259 in the progression of OS.
Methods:
A differentially expressed circRNA, circ_0008259, was screened out by analyzing the expression profile of circRNA in OS tissue. Circ_0008259, miR-21-5p and programmable cell death 4 (PDCD4) mRNA expression levels in OS tissues and cells were detected by qRT-PCR. Cell viability, metastatic potential and apoptosis were evaluated by cell counting kit-8 assay, Transwell and flow cytometry. The targeting relationship between circ_0008259 and miR-21-5p, and miR-21-5p and PDCD4 mRNA was analyzed and probed by bioinformatics analysis and dual-luciferase reporter assay, RNA-binding protein immunoprecipitation assay and RNA-pull down assay. The regulatory effects of circ_0008259 and miR-21-5p on PDCD4 protein expression in OS cells were detected by Western blot assay.
Results:
Circ_0008259 expression and PDCD4 expression were down-regulated and miR-21-5p expression was elevated in the OS tissues and cells. Functional experiments showed that circ_0008259 overexpression significantly inhibited the proliferation and metastatic potential of OS cells and promoted the apoptosis. Besides, PDCD4 was validated as the target gene of miR-21-5p, and circ_0008259 could competitively bind to miR-21-5p, thus up-regulating PDCD4 expression in OS cells.
Conclusions:
Circ_0008259 suppresses OS progression via regulating miR-21-5p/PDCD4 axis.
Insights
Circular RNA circ_0008259 inhibits osteosarcoma progression by regulating the miR-21-5p/PDCD4 axis. This finding offers new insights into osteosarcoma molecular mechanisms and potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma (OS) is a common pediatric bone cancer with poorly understood molecular mechanisms.
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer progression.
- This study investigates the role of circ_0008259 in OS tumorigenesis.
Purpose of the Study:
- To identify and characterize the function of circ_0008259 in osteosarcoma.
- To elucidate the molecular mechanism by which circ_0008259 influences OS progression.
- To explore the regulatory relationship between circ_0008259, miR-21-5p, and PDCD4 in OS.
Main Methods:
- Differential expression analysis of circRNAs in OS tissues to identify circ_0008259.
- Quantitative real-time PCR (qRT-PCR) to measure expression levels of circ_0008259, miR-21-5p, and PDCD4 mRNA.
- In vitro assays including cell counting kit-8, Transwell, and flow cytometry to assess cell viability, metastasis, and apoptosis.
- Bioinformatics analysis, dual-luciferase reporter assays, RNA-binding protein immunoprecipitation, and RNA-pull down assays to determine molecular interactions.
- Western blot to detect protein expression levels.
Main Results:
- Circ_0008259 and PDCD4 expression were downregulated, while miR-21-5p was upregulated in OS tissues and cells.
- Overexpression of circ_0008259 significantly suppressed OS cell proliferation and metastasis while promoting apoptosis.
- PDCD4 was confirmed as a target of miR-21-5p, and circ_0008259 competitively bound to miR-21-5p, thereby increasing PDCD4 expression in OS cells.
Conclusions:
- Circ_0008259 functions as a tumor suppressor in osteosarcoma.
- The circ_0008259/miR-21-5p/PDCD4 axis plays a critical role in regulating OS progression.
- Targeting the circ_0008259/miR-21-5p/PDCD4 pathway may offer a novel therapeutic strategy for osteosarcoma.
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