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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Circular RNA circ_0102049 promotes cell progression as ceRNA to target MDM2 via sponging miR-1304-5p in osteosarcoma
Yan Jin1, Lisen Li2, Tongtong Zhu3
1Department of Ophthalmology, Second Hospital of Jilin University, Changchun, 130000, China.
Abstract:
Osteosarcoma (OS) is known as a tumor that derives from skeletal system with increasing incidence worldwide. This study aimed to explore the effect of a circular RNA (circRNA), circ_0102049, on OS and reveal its potential molecular mechanism. In this work, the expression of circ_0102049 was detected by quantitative real time polymerase chain reaction (qRT-RCR) in both OS specimens and cell lines. The relationship between circ_0102049 level and patients' overall survival was evaluated by Kaplan-Meier curves and Cox regression analysis. Cell proliferation, apoptosis, migration and invasion of U2OS and MG63 cells were measured by cell counting kit-8 (CCK-8), flow cytometry, wound healing and transwell experiments, respectively. In addition, subcellular fractionation, bioinformatics analysis and dual-luciferase reporter assay were utilized to reveal the mechanism of circ_0102049 in OS. Circ_0102049 was overexpressed in both OS specimens and cells. Moreover, the level of circ_0102049 in OS patients was markedly correlated with larger tumor size, pulmonary metastasis and poor prognosis. Circ_0102049 remarkably accelerated cell proliferation, migration and invasion but attenuated cell apoptosis in OS cells analyzed by gain/loss of function experiments. What's more, we identified that circ_0102049 functions as a competing endogenous RNA (ceRNA) to competitively sponge miR-1304-5p to upregulate MDM2 expression at posttranscriptional level, thus mediating the cellular behaviors of OS cells. Collectively, our study provides an innovatively regulatory mechanism of circ_0102049 in OS and points out a new way for OS treatment.
Insights
Circular RNA circ_0102049 is overexpressed in osteosarcoma (OS) and promotes tumor growth and metastasis. It acts as a competing endogenous RNA (ceRNA) by sponging miR-1304-5p to upregulate MDM2, offering a potential therapeutic target for OS.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma (OS) is a primary bone cancer with increasing global incidence.
- Understanding the molecular mechanisms driving OS progression is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of circular RNA circ_0102049 in osteosarcoma (OS).
- To elucidate the molecular mechanism underlying circ_0102049's function in OS.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) for expression analysis.
- Kaplan-Meier curves and Cox regression for survival analysis.
- Cell proliferation (CCK-8), apoptosis (flow cytometry), migration, and invasion assays.
- Subcellular fractionation, bioinformatics, and dual-luciferase reporter assays to determine mechanism.
Main Results:
- Circ_0102049 was significantly overexpressed in OS tissues and cell lines.
- Higher circ_0102049 levels correlated with larger tumor size, pulmonary metastasis, and poorer patient prognosis.
- Gain/loss of function experiments showed circ_0102049 promotes OS cell proliferation, migration, and invasion while inhibiting apoptosis.
- Circ_0102049 acts as a ceRNA for miR-1304-5p, upregulating MDM2 expression and influencing OS cell behavior.
Conclusions:
- Circ_0102049 plays a critical oncogenic role in osteosarcoma.
- The circ_0102049/miR-1304-5p/MDM2 axis represents a novel regulatory pathway in OS.
- Circ_0102049 is a potential therapeutic target for osteosarcoma treatment.
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