Long Noncoding RNA from PVT1 Exon 9 Is Overexpressed in Prostate Cancer and Induces Malignant Transformation and Castration Resistance in Prostate Epithelial Cells.

Gargi Pal,Akintunde Orunmuyi,Onayemi T Onagoruwa,E Oluwabunmi Olapade-Olaopa,Jeannette Huaman,Fayola Levine,Olorunseun O Ogunwobi

doi:10.3390/genes10120964

Abstract

Prostate cancer (PCa) is the most common non-cutaneous cancer and second leading cause of cancer-related death for men in the United States. The nonprotein coding gene locus plasmacytoma variant translocation 1 (PVT1) is located at 8q24 and is dysregulated in different cancers. PVT1 gives rise to several alternatively spliced transcripts and microRNAs. There are at least twelve exons of PVT1, which make separate transcripts, and likely have different functions. Here, we demonstrate that PVT1 exon 9 is significantly overexpressed in PCa tissues in comparison to normal prostate tissues. Both transient and stable overexpression of PVT1 exon 9 significantly induced greater prostate epithelial cell migration, as well as increased proliferation and corresponding proliferating cell nuclear antigen (PCNA) expression. Notably, implantation into mice of a non-tumorigenic prostate epithelial cell line stably overexpressing PVT1 exon 9 resulted in the formation of malignant tumors. Furthermore, PVT1 exon 9 overexpression significantly induced castration resistance. Consequently, PVT1 exon 9 expression is important for PCa initiation and progression, and holds promise as a therapeutic target in PCa.

Highlights

Prostate cancer (PCa) is the second leading cause of cancer-related death in men in the UnitedStates [1]
We previously demonstrated that the transcript from exon 9 of Plasmocytoma variant translocation 1 (PVT1) may be involved in PCa, but the underlying molecular mechanisms were unknown [7]
Expression of PVT1 Exon 9 Is Upregulated in PCa Tissues

Summary

Introduction

Prostate cancer (PCa) is the second leading cause of cancer-related death in men in the UnitedStates [1]. Prostate cancer (PCa) is the second leading cause of cancer-related death in men in the United. According to the American Cancer Society, approximately 174,650 new cases of PCa will be diagnosed in 2019 and will result in 31,620 deaths [2]. Plasmocytoma variant translocation 1 (PVT1) is a long nonprotein-coding. The PVT1 gene locus is comprised of at least twelve exons, which gives rise to several alternatively spliced nonprotein coding transcripts, and encodes six microRNAs: miR-1204, miR-1205, miR-1207-3p, miR-1207-5p, and miR-1208 [7]. PVT1 has been found to be overexpressed in various cancers including breast, lung, colorectal, ovarian, and PCa [8,9,10,11,12].

Methods

Results

Conclusion