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LncRNA-TMPO-AS1 promotes apoptosis of osteosarcoma cells by targeting miR-329 and regulating E2F1
1Department of Laboratory, Second Affiliated Hospital of Dalian Medical University, Dalian, China. liulili198102@163.com.
Objective:
This study aims to explore the clinical value and mechanism of lncRNA-TMPO-AS1 in osteosarcoma.
Patients And Methods:
We collected 51 samples of cancer tissues and 51 samples of matched adjacent tissues from 51 patients with osteosarcoma undergoing surgery in our hospital from February 2018 to February 2019. The expression of TMPO-AS1 in tissue samples was tested to analyze its value in the diagnosis and prognosis prediction of osteosarcoma. We transfected osteosarcoma cells with stable and transient vectors containing overexpressed or inhibited genes. Then, we measured cell proliferation by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay, cell invasion by transwell assay, and cell apoptosis by flow cytometry (FCM). The relationship between TMPO-AS1 and miR-329 or between miR-329 and E2F1 was determined by the Dual-Luciferase reporter (DLR) assay.
Results:
TMPO-AS1 was up-regulated in osteosarcoma cells. Serum TMPO-AS1 could work as a diagnostic marker for osteosarcoma, with an area under the receiver operating characteristic (ROC) curve (AUC) of more than 0.8. Osteosarcoma cells were transfected with siRNA-TMPO-AS1, pcDNA3.1-TMPO-AS1, miR-329-mimics, and miR-329-inhibitor. The results revealed that inhibited TMPO-AS1/overexpressed miR-329/inhibited E2F1 suppressed the proliferation and invasion of osteosarcoma cells and enhanced cell apoptosis. The DLR assay demonstrated that TMPO-AS1 could target miR-329 and miR-329 could target E2F1. In vitro experiments revealed that TMPO-AS1 could regulate the progression of epithelial-mesenchymal transition (EMT) in osteosarcoma through the miR-329/E2F1 axis.
Conclusions:
TMPO-AS1 can function as a diagnostic and prognostic marker for osteosarcoma. LncRNA-TMPO-AS1 can promote apoptosis of osteosarcoma cells by targeting miR-329 and regulating E2F1, which is a potent treatment option for osteosarcoma.
Insights
Long non-coding RNA TMPO-AS1 is elevated in osteosarcoma and serves as a diagnostic marker. Targeting TMPO-AS1 promotes osteosarcoma cell apoptosis via the miR-329/E2F1 pathway, offering a potential therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma is a primary bone malignancy with limited treatment options.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development and progression.
- The specific role and mechanism of lncRNA-TMPO-AS1 in osteosarcoma remain largely unexplored.
Purpose of the Study:
- To investigate the clinical significance of lncRNA-TMPO-AS1 in osteosarcoma diagnosis and prognosis.
- To elucidate the molecular mechanism underlying the function of lncRNA-TMPO-AS1 in osteosarcoma progression.
- To explore the potential of targeting lncRNA-TMPO-AS1 as a therapeutic strategy for osteosarcoma.
Main Methods:
- Analysis of TMPO-AS1 expression in osteosarcoma tissues and adjacent normal tissues from 51 patients.
- In vitro functional assays including MTT, Transwell invasion, and flow cytometry to assess cell proliferation, invasion, and apoptosis.
- Luciferase reporter assays to confirm the targeting relationships between TMPO-AS1, miR-329, and E2F1.
- Cell transfection with vectors for gene overexpression or inhibition.
Main Results:
- TMPO-AS1 expression was significantly upregulated in osteosarcoma tissues compared to adjacent tissues.
- Serum TMPO-AS1 demonstrated diagnostic value for osteosarcoma with an AUC > 0.8.
- Inhibition of TMPO-AS1 or overexpression of miR-329 suppressed osteosarcoma cell proliferation and invasion while promoting apoptosis.
- TMPO-AS1 targets miR-329, which in turn targets E2F1, regulating epithelial-mesenchymal transition (EMT) in osteosarcoma.
Conclusions:
- lncRNA-TMPO-AS1 serves as a valuable diagnostic and prognostic biomarker for osteosarcoma.
- TMPO-AS1 promotes osteosarcoma cell proliferation and invasion by targeting the miR-329/E2F1 axis.
- Targeting lncRNA-TMPO-AS1 presents a promising therapeutic avenue for osteosarcoma treatment.
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