In the present study, a TF-based robust MYC-estrogen related receptor α-regulatory factor X5 (MYC-ESRRA-RFX5) signature was developed for predicting the survival of patients with renal cell carcinoma.
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.
Our studies demonstrate that MYC overexpression causes RCC and points to the inhibition of glutamine metabolism as a potential therapeutic approach for the treatment of this disease.
Most RCC result from Von Hippel-Lindau (VHL) tumor suppressor loss-of-function and subsequent gain-of-function of the oncogenic HIF-2alpha/c-MYC pathway.
Our results suggest for the first time that let-7a acts as a tumor suppressor in RCC cell lines by down-regulating c-myc and c-myc target genes such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and the miR17-92 cluster, which is accompanied by proliferation inhibition and cell cycle arrest.
The importance of MYC activation was confirmed by both pharmacologic and short interfering RNA-mediated inhibition of active Myc signaling in a cell line model of type 2 papillary RCC.
PFG analysis of DNA containing the t(3;8) rearrangement shows that the breakpoint is not located in the mapped region, making it unlikely that MYC is involved in this form of renal cell carcinoma.
The possible role that the relocation of c-myc might have on the development of renal carcinoma in carriers of this 3;8 translocation was further studied by analysis of the region surrounding the c-myc gene.
The translocated c-myc gene should provide a probe to the chromosome 3p14 region, which appears to be important not only in renal cell carcinoma but also in small cell carcinoma of the lung.