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Silencing hsa_circRNA_0008035 exerted repressive function on osteosarcoma cell growth and migration by upregulating
Gu Gong1, Zhifeng Han2, Wenjun Wang1
1Department of Orthopaedics, China-Japan Union Hospital of Jilin University , Changchun, Jilin, China.
Abstract:
Traditionally, circular RAN hsa_circ_0008035 was proven to function as a tumor inhibitor in gastric cancer. Nevertheless, much less was known about hsa_circ_0008035 in osteosarcoma (OSA). This project was undertaken to assess the role of hsa_circ_0008035 in OSA. Hsa_circ_0008035 level in serum of OSA patients, OSA tissues and cell lines were measured by reverse transcription-quantitative PCR. After downregulation or overexpression of hsa_circ_0008035, cell proliferation, apoptosis and migration were tested in MG63, SAOS-2 or hFOB1.19 cells. Meanwhile, the expression level of miR-375 was analyzed. The binding between hsa_circ_0008035 and miR-375 was confirmed using bioinformatics and luciferase assay. Subsequently, the effects of miR-375 inhibition on MG63 cell growth and migratory potential were reevaluated. Eventually, the activating status of Notch pathway was assessed by Western blot. Our results demonstrated that hsa_circ_0008035 was overexpressed in serum of OSA patients, OSA tissues and cells. Silencing hsa_circRNA_0008035 impeded OSA cell growth and migration, while hsa_circ_0008035 facilitated cell behaviors of hFOB1.19 cells. Additionally, hsa_circ_0008035 negatively modulated miR-375 expression. Meanwhile, miR-375 inhibition overturned the suppressive effects of silencing hsa_circRNA_0008035 on OSA cell behaviors. Furthermore, silencing hsa_circ_0008035 perturbed Notch pathway by adjusting miR-375 expression. In conclusion, silencing hsa_circRNA_0008035 exerted repressive function on OSA cell growth and migration and Notch pathway by accelerating miR-375.
Insights
Circular RNA hsa_circ_0008035 promotes osteosarcoma progression by inhibiting miR-375 and activating the Notch pathway. Silencing this circRNA suppresses tumor growth and migration.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNA hsa_circ_0008035 is a known tumor inhibitor in gastric cancer.
- Its role in osteosarcoma (OSA) remains largely unexplored.
Purpose of the Study:
- To investigate the function of hsa_circ_0008035 in osteosarcoma.
- To elucidate the underlying molecular mechanisms involving miR-375 and the Notch pathway.
Main Methods:
- Quantitative reverse transcription PCR to measure hsa_circ_0008035 levels in patient samples and cell lines.
- Cell proliferation, apoptosis, and migration assays following hsa_circ_0008035 or miR-375 manipulation.
- Bioinformatics and luciferase assays to confirm binding between hsa_circ_0008035 and miR-375.
- Western blot analysis to assess Notch pathway activation.
Main Results:
- hsa_circ_0008035 was significantly overexpressed in OSA patient serum, tissues, and cell lines.
- Silencing hsa_circ_0008035 inhibited OSA cell proliferation and migration, while its overexpression promoted these behaviors in normal cells.
- hsa_circ_0008035 negatively regulated miR-375 expression, and miR-375 inhibition reversed the effects of hsa_circ_0008035 silencing.
- Silencing hsa_circ_0008035 suppressed the Notch pathway by modulating miR-375.
Conclusions:
- hsa_circ_0008035 acts as an oncogene in osteosarcoma, promoting cell growth and migration.
- The hsa_circ_0008035/miR-375 axis plays a crucial role in OSA progression.
- Silencing hsa_circ_0008035 inhibits osteosarcoma by targeting the Notch pathway via miR-375.
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