Oncogenic Role of PVT1 and Therapeutic Implications

Abstract

PVT1, a long non-coding RNA has been implicated in a variety of human cancers. Recent advancements have led to increasing discovery of the critical roles of PVT1 in cancer initiation and progression. Novel insight is emerging about PVT1's mechanism of action in different cancers. Identifying and understanding the variety of activities of PVT1 involved in cancers is a necessity for the development of PVT1 as a diagnostic biomarker or therapeutic target in cancers where PVT1 is dysregulated. PVT1's varied activities include overexpression, modulation of miRNA expression, protein interactions, targeting of regulatory genes, formation of fusion genes, functioning as a competing endogenous RNA (ceRNA), and interactions with MYC, among many others. Furthermore, bioinformatic analysis of PVT1 interactions in cancers has aided understanding of the numerous pathways involved in PVT1 contribution to carcinogenesis in a cancer type-specific manner. However, these recent findings show that there is much more to be learned to be able to fully exploit PVT1 for cancer prognostication and therapy. In this review, we summarize some of the latest findings on PVT1's oncogenic activities, signaling networks and how targeting these networks can be a strategy for cancer therapy.

Long Noncoding RNA PVT1 Is Regulated by Bromodomain Protein BRD4 in Multiple Myeloma and Is Associated with Disease Progression

“…Our observation of the high expression of PVT1 and MYC in MM cells compared with normal plasma cells is consistent with those of previous studies [ 17 ]. Many studies have illustrated that PVT1 levels are higher in many cancers with an increased MYC expression than in normal tissues and are associated with a poor prognosis [ 16 , 23 , 24 , 25 ]. Tissue microarray analysis of primary tumors indicated a high correlation between PVT1 and MYC expression, providing strong evidence for cooperation between PVT1 and MYC in different human cancers [ 29 ].…”

“…These results suggested that a high level of PVT1 might be associated with a prognosis of relapse and drug resistance. An association between high PVT1 expression and poor prognosis was reported in several cancers [ 16 , 23 , 25 ]. The involvement of PVT1 in resistance to anticancer drugs through several pathways was documented [ 24 , 34 ].…”

“…PVT1 is located at the 8q24 locus adjacent to MYC [ 18 ], which is highly expressed in many types of cancer and plays an important role in carcinogenesis [ 19 , 20 ]. PVT1 is elevated in MM [ 5 , 21 ] and coamplified with MYC in many cancers [ 18 ]; there is an association between PVT1 expression level and poor prognosis in many cancers [ 16 , 17 , 22 , 23 , 24 ]. High-level amplification and/or overexpression of PVT1 is associated with an invasive phenotype of breast cancer and reduced survival time in ovarian cancer patients [ 25 ].…”

Crosstalk of lncRNA and Cellular Metabolism and Their Regulatory Mechanism in Cancer

“…As indicated by a previous study, TUG1 is associated with HK2-mediated glycolysis in osteosarcoma [33]. LncRNA PVT1 plays an oncogenic role in multiple cancers [34]. The overexpression of PVT1 enhances glucose metabolism via modulation of the miR-497/HK2 axis in osteosarcoma [35].…”

<p>Long Noncoding RNA PVT1 Promotes Prostate Cancer Metastasis by Increasing NOP2 Expression via Targeting Tumor Suppressor MicroRNAs</p>

“…Non-coding RNAs (ncRNAs) are RNA transcripts from genes not encoding for a protein. 9 Murine NOP2 is homologous to yeast protein NOP2p and human NOP2 (also named NSUN1 or P120). 10 NOP2 belongs to the NOP2/SUN (NSUN) RNA-methyltransferase family, which includes six other members: NSUN2 through NSUN7.…”