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Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
Hsa_circ_0000285 functions as a competitive endogenous RNA to promote osteosarcoma progression by sponging
Zhicai Zhang1, Feifei Pu1, Baichuan Wang1
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Insights
Circular RNA (circ-0000285) promotes osteosarcoma progression by enhancing cell proliferation and migration. This effect is mediated through the circ-0000285/miRNA-599/TGFB2 axis, offering new insights into osteosarcoma pathogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) play a role in disease pathogenesis.
- Osteosarcoma is a bone cancer where circRNAs are implicated.
- hsa_circ_0000285 (circ-0000285) is upregulated in osteosarcoma and affects cell behavior.
Purpose of the Study:
- To investigate the role of circ-0000285 in osteosarcoma cell proliferation and migration.
- To elucidate the molecular mechanism involving circ-0000285, miRNA-599, and TGFB2 in osteosarcoma progression.
Main Methods:
- Gene expression analysis using qRT-PCR to compare circ-0000285 levels in osteosarcoma and normal cells.
- Dual-luciferase reporter gene assay and RIP assay to confirm binding interactions between circ-0000285, miRNA-599, and TGFB2.
- EdU assay and transwell migration assay to evaluate the functional impact of circ-0000285 and miRNA-599 on cell proliferation and migration.
Main Results:
- circ-0000285 was found to be highly expressed in osteosarcoma cell lines compared to normal osteoblasts.
- circ-0000285 and TGFB2 were confirmed to directly bind to miRNA-599.
- Overexpression of circ-0000285 increased osteosarcoma cell proliferation and migration, effects reversed by miRNA-599 overexpression.
Conclusions:
- The circ-0000285/miRNA-599/TGFB2 axis is a critical regulator of osteosarcoma cell proliferation and migration.
- This axis provides a novel perspective for understanding osteosarcoma pathogenesis.
- circ-0000285 may serve as a potential therapeutic target for osteosarcoma.
Abstract:
Circular RNA (circRNA) is important in the pathogenesis of many diseases. By analyzing the GSE96964 microarray, hsa_circ_0000285 (circ-0000285) was found to be highly expressed in osteosarcoma. Recent studies have shown that circ-0000285 is capable of regulating proliferative and migratory potentials. Here, we investigated the potential functions in regulating osteosarcoma cells to proliferate and migrate. First of all, qRT-PCR data revealed a higher level of circ-0000285 in osteosarcoma cell lines relative to normal osteoblasts. Through dual-luciferase reporter gene assay and RIP assay, we confirmed that both circ-0000285 and TGFB2 could directly bind to miRNA-599. Regulatory effects of circ-0000285 and miRNA-599 on proliferative and migratory potentials were evaluated by EdU assay and transwell migration assay. It is indicated that circ-0000285 overexpression enhanced the proliferative and migratory potentials of osteosarcoma, which could be reversed by miRNA-599 overexpression. This study revealed a vital role of circ-0000285/miRNA-599/TGFB2 axis in regulating the progression of osteosarcoma, providing a novel perspective for clarifying its pathogenesis.
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