Long noncoding RNA PVT1 promotes breast cancer proliferation and metastasis by binding miR-128-3p and UPF1

Shuiyi Liu,Weiqun Chen,Hui Hu,Tianzhu Zhang,Tangwei Wu,Xiaoyi Li,Yong Li,Qinzhi Kong,Hongda Lu,Zhongxin Lu

doi:10.1186/s13058-021-01491-y

Abstract

BackgroundMounting evidence supports that long noncoding RNAs (lncRNAs) have critical roles during cancer initiation and progression. In this study, we report that the plasmacytoma variant translocation 1 (PVT1) lncRNA is involved in breast cancer progression.MethodsqRT-PCR and western blot were performed to detect the gene and protein expression. Colony formation would healing and transwell assays were used to detect cell function. Dual-luciferase reporter assay and RNA pull-down experiments were used to examine the mechanisms interaction between molecules. Orthotopic mouse models were established to evaluate the influence of PVT1 on tumor growth and metastasis in vivo.ResultsPVT1 is significant upregulated in breast cancer patients’ plasma and cell lines. PVT1 promotes breast cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, PVT1 upregulates FOXQ1 via miR-128-3p and promotes epithelial–mesenchymal transition. In addition, PVT1 binds to the UPF1 protein, thereby inducing epithelial–mesenchymal transition, proliferation and metastasis in breast cancer cells.ConclusionPVT1 may act as an oncogene in breast cancer through binding miR-128-3p and UPF1 and represents a potential target for BC therapeutic development.

Highlights

Mounting evidence supports that long noncoding RNAs have critical roles during cancer initiation and progression
Recent research has revealed that plasmacytoma variant translocation 1 (PVT1) is up regulated in nasopharyngeal carcinoma tissues and its overexpression predicts a poor prognosis for Nasopharyngeal carcinoma (NPC) patients
These results suggested that PVT1 is a candidate predictor for breast cancer (BC) diagnosis and staging assessment

Summary

Introduction

Mounting evidence supports that long noncoding RNAs (lncRNAs) have critical roles during cancer initiation and progression. We report that the plasmacytoma variant translocation 1 (PVT1) lncRNA is involved in breast cancer progression. Long noncoding RNAs (lncRNAs), previously regarded as transcriptional noise, have gradually become a focus of research in various diseases, especially in cancer [2, 3]. The plasmacytoma variant translocation 1 (PVT1) is an oncogenic lncRNA, located at the 8q24 region, was discovered in murine plasmacytoma in 1985 [7]. PVT1 is upregulated in numerous cancers, functioning as an oncogene in malignant progression [8, 9]. Loss-of-function experiments support that PVT1 regulates cell apoptosis by influencing the DNA damage repair pathway after radiation, suggesting that targeting PVT1 may be a potential strategy for NPC therapy [11]. More data are required to elucidate the functions of PVT1 in tumor progression

Methods

Results

Discussion

Conclusion