Long non-coding RNA PVT1 promotes osteosarcoma development by acting as a molecular sponge to regulate miR-195.

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.

• Authors: Quan Zhou, Fengli Chen, Jiali Zhao, Baojun Li, Yong Liang, Wei Pan, Shaoxian Zhang, Xinhong Wang, Donghui Zheng
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 50 Pg. 82620-82633 (Dec 13 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27813492 (Publication Type: Journal Article)

Chemical References

• BCL2 protein, human
• CCND1 protein, human
• MIRN195 microRNA, human
• MicroRNAs
• PVT1 long-non-coding RNA, human
• Proto-Oncogene Proteins c-bcl-2
• RNA, Long Noncoding
• Cyclin D1
• FASN protein, human
• Fatty Acid Synthase, Type I

Topics

• Apoptosis
• Bone Neoplasms (genetics, metabolism, pathology, surgery)
• Cell Cycle Checkpoints
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Cyclin D1 (genetics, metabolism)
• Fatty Acid Synthase, Type I (genetics, metabolism)
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Humans
• MicroRNAs (genetics, metabolism)
• Neoplasm Invasiveness
• Oligonucleotide Array Sequence Analysis
• Osteosarcoma (genetics, metabolism, pathology, surgery)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• RNA Interference
• RNA, Long Noncoding (genetics, metabolism)
• Signal Transduction
• Time Factors
• Transfection