Abstract
A growing body of evidence has indicated that long non-coding RNAs (lncRNAs) serve as competing endogenous RNAs (ceRNAs) during oncogenesis. In this study, the qRT-PCR results indicated that the lncRNA PVT1 is overexpressed in osteosarcoma and decreased the survival rate of osteosarcoma patients. MTT and clonal colony formation assays were used to detect the effect of PVT1 on proliferation, and flow cytometry was performed to assess apoptosis and the cell cycle. A Transwell assay was used to analyze migration and invasion. The results revealed that silencing PVT1 by siRNA inhibited proliferation, migration and invasion and promoted apoptosis and cell cycle arrest in osteosarcoma cells. Furthermore, a gene microarray was used to screen differentially expressed miRNAs associated with PVT1. The interaction between PVT1 and miRNAs was then analyzed by qRT-PCR and luciferase reporter gene assay. We found that PVT1 negatively regulated miR-195 in osteosarcoma cells. Simultaneously, we found that silencing PVT1 by siRNA suppressed proliferation, migration and invasion and promoted cell cycle arrest and apoptosis via miR-195 in osteosarcoma cells. Moreover, silencing PVT1 by siRNA inhibited BCL2, CCND1, and FASN protein expression via miR-195 in osteosarcoma cells, and BCL2 inhibited the si-PVT1#1-induced apoptosis of U2OS cells. CCND1 inhibited the cell cycle arrest of U2OS cells induced by si-PVT1#1. FASN promoted the invasiveness U2OS cells, which was inhibited by si-PVT1#1. Therefore, our study demonstrated that PVT1 may be a therapeutic target for treatment of osteosarcoma.
Highlights
Osteosarcoma is a malignant primary bone tumor that is lethal to primarily children and adolescents [1, 2]
The mRNA expression level of PVT1 was measured by Quantitative real-time reverse transcription PCR (qRT-PCR) and increased in osteosarcoma tissues compared with corresponding noncancerous tissues (Figure 1A)
The results showed that the mRNA expression level of PVT1 was higher in metastatic osteosarcoma tissues than primary osteosarcoma tissues (P < 0.05) (Figure 1D)
Summary
Osteosarcoma is a malignant primary bone tumor that is lethal to primarily children and adolescents [1, 2]. The incidence of osteosarcoma is moderate, approximately 10 to 26 new cases per million worldwide annually [3]. Osteosarcoma is highly aggressive and rapidly metastasizes, which results in poor survival [4]. The 5-year survival rate of osteosarcoma patients, most of whom died of lung metastases, was less than 20% in the first half of the 20th century [4, 5]. Surgery, chemotherapy, and palliative radiotherapy are the main treatment methods for patients with osteosarcoma. The efficacy of conventional therapy is limited, and osteosarcoma diagnosis is restricted because the molecular and functional mechanisms of this disease are poorly understood. Further research is needed to identify effective biomarkers and molecular targets
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