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TRPS1 and YAP1 Regulate Cell Proliferation and Drug Resistance of Osteosarcoma via Competitively Binding to the
Jinyu Zhang1, Xiang Ma1, Ruiqi Zhou1
1Department of Orthopaedics, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming 650118, People's Republic of China.
Introduction:
The yes-associated protein (YAP) and trichorhinophalangeal syndrome 1 (TRPS1) have been reported to account for the pathogenesis of cancers and may play an important role in osteosarcoma (OS). This study intended to investigate the modulatory effect and relationship of TRPS1 and YAP1 in OS cells.
Methods:
The expression difference of YAP1 and TRPS1 in OS cells was measured. Then, the effect of circTADA2A silence on YAP1 and TRPS1 expression as well as OS proliferation and drug resistance was estimated.
Results:
TRPS1 and YAP1 were upregulated in OS cell lines, and TRPS1 and YAP1 were highly expressed in MG63 and U2OS cells, respectively. The cell proliferation of MG63 was lower than that of U2OS, but the opposite result was observed in the presence of cisplatin (DDP). CircTADA2A was upregulated while miR-129-5p was downregulated in MG63 and U2OS cells compared. Besides, circTADA2A knockdown inhibited cell proliferation and reduced DDP resistance in both MG63 and U2OS. MiR-129-5p was increased but TRPS1 and YAP1 were decreased by circTADA2A knockdown. Meanwhile, circTADA2A knockdown reduced TRPS1 protein expression but enhanced phosphorylated (p)-YAP1. In xenograft OS tumor mice, circTADA2A knockdown inhibited tumor growth in the absence or presence of DDP. Finally, miR-129-5p could bind to circTADA2A, TRPS1 and YAPS.
Discussion:
CircRNA TADA2A could target miR-129-5p, which was competitively bound by TRPS1 and YAP1, thereby regulating OS cell proliferation and drug resistance.
Insights
CircRNA TADA2A targets miR-129-5p, affecting osteosarcoma (OS) cell growth and drug resistance by interacting with TRPS1 and YAP1 proteins. This finding offers potential therapeutic strategies for OS treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The yes-associated protein (YAP) and trichorhinophalangeal syndrome 1 (TRPS1) are implicated in cancer development.
- Their specific roles in osteosarcoma (OS) pathogenesis require further elucidation.
Purpose of the Study:
- To investigate the modulatory effects and interrelationship of TRPS1 and YAP1 in OS cells.
- To explore the role of circTADA2A in regulating these proteins and impacting OS progression.
Main Methods:
- Quantitative analysis of YAP1 and TRPS1 expression in OS cell lines.
- Assessment of circTADA2A knockdown effects on OS cell proliferation, drug resistance (cisplatin/DDP), and target gene expression (TRPS1, YAP1, miR-129-5p).
- In vivo studies using xenograft OS tumor mouse models.
Main Results:
- TRPS1 and YAP1 were upregulated in OS cells, with differential expression patterns.
- CircTADA2A knockdown inhibited OS cell proliferation and DDP resistance, increasing miR-129-5p while decreasing TRPS1 and YAP1.
- CircTADA2A knockdown suppressed tumor growth in vivo and affected TRPS1 protein and p-YAP1 levels.
Conclusions:
- CircRNA TADA2A acts as a molecular sponge for miR-129-5p.
- TRPS1 and YAP1 competitively bind to miR-129-5p, influencing OS cell proliferation and drug resistance.
- CircTADA2A plays a significant role in OS progression and chemoresistance.
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