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TNK2-AS1 upregulated by YY1 boosts the course of osteosarcoma through targeting miR-4319/WDR1
Weitao Yao1, Qiang Yan1, Xinhui Du1
1Department of Bone and Soft Tumor, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Abstract:
Mounting research papers have suggested that long non-coding RNAs (lncRNAs) elicit important functions in the progression of osteosarcoma (OS). This study focused on the role of TNK2-AS1 in OS. TNK2-AS1 was powerfully expressed in OS tissues and cell lines. In addition, TNK2-AS1 downregulation inhibited proliferative, migratory, and invasive capacities while promoting apoptosis in OS cells. miR-4319 was removed by TNK2-AS1 and therefore TNK2-AS1 elevated WDR1 expression in OS cells. miR-4319 had an inhibitory influence on OS progression, while WDR1 was a contributor to OS progression. Rescue assays certified that TNK2-AS1 promoted malignant phenotypes in vitro and the growth in vivo of OS cells by upregulating WDR1. In depth, we found that YY1 accelerated the transcription of TNK2-AS1 in OS cells, and that its role in OS also depended on TNK2-AS1-regulated WDR1. In conclusion, TNK2-AS1 was positively modulated by YY1 and aggravated the development of OS by 'sponging' miR-4319 to elevate WDR1. The findings highlighted that TNK2-AS1 might be a promising target for the treatment of OS.
Insights
The long non-coding RNA TNK2-AS1 promotes osteosarcoma (OS) progression by increasing WDR1 expression. Targeting TNK2-AS1 may offer a new therapeutic strategy for OS patients.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) play critical roles in cancer development.
- Osteosarcoma (OS) is a primary bone malignancy with significant metastatic potential.
- The specific functions of lncRNAs in OS progression require further elucidation.
Purpose of the Study:
- To investigate the role and mechanism of TNK2-AS1 in osteosarcoma (OS).
- To explore the regulatory relationship between TNK2-AS1, miR-4319, and WDR1 in OS.
- To identify potential therapeutic targets for OS treatment.
Main Methods:
- Quantitative real-time PCR to assess TNK2-AS1 expression in OS tissues and cell lines.
- Cell proliferation, migration, invasion, and apoptosis assays to evaluate TNK2-AS1 function.
- Western blotting and luciferase reporter assays to confirm molecular interactions.
- In vivo tumor growth assays in mouse models.
Main Results:
- TNK2-AS1 expression was significantly upregulated in OS tissues and cell lines.
- Downregulation of TNK2-AS1 suppressed OS cell proliferation, migration, and invasion, while promoting apoptosis.
- TNK2-AS1 acted as a molecular sponge for miR-4319, leading to increased WDR1 expression.
- YY1 transcriptionally activated TNK2-AS1, contributing to OS progression via the TNK2-AS1/miR-4319/WDR1 axis.
Conclusions:
- TNK2-AS1 promotes osteosarcoma progression by upregulating WDR1 through sponging miR-4319.
- The YY1/TNK2-AS1/miR-4319/WDR1 pathway is crucial for OS development.
- TNK2-AS1 represents a potential therapeutic target for osteosarcoma.
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