A pan-cancer analysis of MYC-PVT1 reveals CNV-unmediated deregulation and poor prognosis in renal carcinoma

Abstract

The PVT1 lncRNA has recently been involved in tumorigenesis by affecting the protein stability of the MYC proto-oncogene. Both MYC and PVT1 reside in a well-known cancer-risk locus and enhanced levels of their products have been reported in different human cancers. Nonetheless, the extension and relevance of the MYC-PVT1 deregulation in tumorigenesis has not yet been systematically addressed.Here we performed a pan-cancer analysis of matched copy number, transcriptomic, methylation, proteomic and clinicopathological profiles for almost 7000 patients from 17 different cancers represented in the TCGA cohorts. Among all cancers types, kidney renal clear cell carcinoma (KIRC) showed the strongest upregulation of PVT1 and increased levels of both MYC and PVT1 correlated with the clinical outcome. PVT1 misregulation in KIRC is mostly associated to promoter hypomethylation rather than locus amplification. Furthermore, we found an association between MYC levels and PVT1 expression, which impacted on MYC-target genes.Collectively, our study discloses the role of PVT1 as a novel prognostic factor and as a molecular target for novel therapeutic interventions in renal carcinoma.

Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma

“…Our data indicate convergent genomic (copy number) and epigenetic (DNA methylation) mechanisms of PVT1 regulation in UM. Overall, our observations for PVT1 in M3-UM are consistent with it being highly regulated by DNA methylation in renal cell carcinoma (Posa et al, 2016), acting as an independent oncogene and enhancing MYC protein levels/activity (Tseng et al, 2014). In addition, we identified other coding and non-coding genes that are associated with recurrent SCNA in UM and are candidates for further functional studies.…”

Overexpression of LncRNA PVT1 Predicts Advanced Clinicopathological Features and Serves as an Unfavorable Risk Factor for Survival of Patients with Gastrointestinal Cancers

“…Among the 15 articles, the digestive system malignancies assessed in these studies included esophageal carcinoma (2 articles) [39, 44], gastric cancer (6 articles) [22, 33, 38, 40-42], colorectal cancer (2 articles) [20, 37], hepatocellular carcinoma (2 articles) [21, 34], pancreatic cancer (3 articles) [35, 36, 43]. Among the eligible articles, one came from Japan [20], one came from Portugal [36] and the rest of 13 articles were came from China [21-22, 33-35, 37-44]. The participants in all the studies could be classified into high PVT1 expression group and low PVT1 expression group.…”

Long non-coding RNAs in renal cell carcinoma: A systematic review and clinical implications

“…As shown in Table 3 , decreased expression of lncRNA NONHSAT123350, CADM1-AS1, TCL6 and lnc-ZNF180-2 is correlated with poorer prognosis of RCC patients [ 38 , 60 , 65 , 68 ]. On the other hand, overexpression of SPRY4-IT1, RCCRT1, MALAT1, Linc00152 and PVT1 shows a poor prognosis, as well [ 44 , 49 – 52 , 59 ].…”