Oncotarget

Research Papers:

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

Quan Zhou, Fengli Chen, Jiali Zhao, Baojun Li, Yong Liang, Wei Pan, Shaoxian Zhang, Xinhong Wang and Donghui Zheng _

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Oncotarget. 2016; 7:82620-82633. https://doi.org/10.18632/oncotarget.13012

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Abstract

Quan Zhou1,*, Fengli Chen2,*, Jiali Zhao1, Baojun Li4, Yong Liang3, Wei Pan1, Shaoxian Zhang1, Xinhong Wang1, Donghui Zheng3

1Department of Orthopaedics, Huai’an Hospital Affiliated of Xuzhou Medical University and Huai’an Second Hospital, Huai’an 223002, Jiangsu, China

2Department of Central Laboratory, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an 223002, Jiangsu, China

3Department of Central Laboratory and Department of Nephrology, Huai’an Hospital Affiliated of Xuzhou Medical University and Huai’an Second Hospital, Huai’an 223002, Jiangsu, China

4Department of Joint Surgery, Second People’s Hospital of Hunan Province, Changsha 410007, Hunan, China

*These authors contributed equally to this work

Correspondence to:

Donghui Zheng, email: zhengdonghui2016@126.com

Keywords: PVT1, miR-195, osteosarcoma, proliferation, invasion

Received: July 07, 2016     Accepted: September 29, 2016     Published: November 02, 2016

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.


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