Mp99-19 targeting lncrna-gas5 suppresses castration resistant prostate cancer cell growth via interaction and suppression androgen receptor (ar) transactivation

These data suggests that PVT1 can potentiate MYC in human cancers.CRISPR-cas9 mediated deletion of PVT1 in HCT116 impaired tumor formation in xenografts, and significantly reduced MYC levels.Additionally, we have identified the putative functional domain of PVT1 which confers its oncogenic potential.We have recently discovered that the exon 2 of PVT1 can undergo 'backsplicing' and form circular RNA of 410 bases (CircPVT1).This CircPVT1 is more abundant in MYC-driven cancer cell lines.Though PVT1 is known as a long non-coding RNA, we found that CircPVT1 can form an open reading frame (ORF) of 104 amino acids, which we have annotated as PVT1 encoded protein upon circularization (PEPc).While CRISPR-Cas9 mediated deletion of PVT1 exon 2 results into decreased MYC levels and reduced transformation potential in MYC-driven cancer cells, PEPc can independently augment MYC when added exogenously to LNCaP cells, and increase their transformation potential.CONCLUSIONS: These results suggest that PEPc may play a key role in boosting MYC levels in metastatic prostate cancers.We propose that the dependence of high levels of MYC on PVT1 provides a much-needed therapeutic window against MYC protein, known to be refractory to small molecule inhibition.