PVT1 Exon 9: A Potential Biomarker of Aggressive Prostate Cancer?

Abstract

Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest source of cancer-related mortality in males of African ancestry (MoAA). Interestingly, this has been shown to be associated with single nucleotide polymorphisms around regions 2 and 3 of the 8q24 human chromosomal region. The non-protein coding gene locus Plasmacytoma Variant Translocation 1 (PVT1) is located at 8q24 and is overexpressed in PCa and, therefore, is also a candidate biomarker to explain the well-known disparity in this group. PVT1 has at least 12 exons that make separate transcripts which may have different functions, all of which are at present unknown in PCa. Our aim was to determine if any PVT1 transcripts play a role in aggressiveness and racial disparity in PCa. We used a panel of seven PCa cell lines including three derived from MoAA. Ribonucleic acid extraction, complementary deoxyribonucleic acid synthesis, and quantitative polymerase chain reaction (qPCR) were performed to evaluate expression of all 12 PVT1 exons. Each qPCR was performed in quadruplicates. At least four separate qPCR experiments were performed. Expression of PVT1 exons was inconsistent except for exon 9. There was no significant difference in exon 9 expression between cell lines derived from Caucasian males (CM), and an indolent cell line derived from MoAA. However, exon 9 expression in the aggressive MDA PCa 2b and E006AA-hT cell lines derived from MoAA was significantly higher than in other cell lines. Consequently, we observed differential expression of exon 9 of PVT1 in a manner that suggests that PVT1 exon 9 may be associated with aggressive PCa in MoAA.

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

“…Plasmocytoma variant translocation 1 (PVT1) is a long nonprotein-coding gene located at the 8q24 human chromosomal region and is commonly dysregulated in PCa [5,6]. 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].…”

Interactions ofPVT1andCASC11on Prostate Cancer Risk in African Americans

“…PVT1 is overexpressed in prostate cancer tumor tissues and is associated with regulating tumor growth (8,9). It has been shown that PVT1 exon 9 is significantly overexpressed in aggressive prostate cancer cell lines derived from AA men (10). PVT1 is a long noncoding RNA and is the host to a cluster of miRNAs (such as miR-1204, miR-1205, and miR-1206; refs.…”

Oncogenic Role of PVT1 and Therapeutic Implications

“…Knock down of PVT1 exons 4A and 4B in turn did not yield similar effects. The Ogunwobi laboratory also reported that PVT1 exon 9 is significantly overexpressed in prostate cancer cell lines derived from men of African Ancestry (MoAA) (94) (Figure 3). This observation was made from comparing the relative expression of PVT1 exons in different cell lines derived from men of different ethnic and racial backgrounds.…”