LncRNA PVT1 Is a Poor Prognosticator and Can Be Targeted by PVT1 Antisense Oligos in Gastric Adenocarcinoma

SIMPLE SUMMARY: LncRNA-PVT1 is upregulated in a variety of human cancers, to validate LncRNA-PVT1 expression in gastric adenocarcinoma (GAC), RNA-SCOPE of LncRNA-PVT1 was performed in a large cohort in GAC TMAs. LncRNA-PVT1 is upregulated in GAC tissues and correlated with larger tumor size, invasion depth and lymph node metastasis. In the peritoneal metastasis ascites cells of GAC, LncRNA-PVT1 level is also upregulated compared to normal adjacent tissues. LncRNA-PVT1 is a poor prognosticator as well as therapeutic target in GAC. Targeting PVT1 using PVT1 ASOs suppressed tumor proliferation and invasion in both vitro and vivo, thus provide a novel therapeutic strategy for GAC. ABSTRACT: Gastric adenocarcinoma (GAC) is inherently resistant or becomes resistant to therapy, leading to a poor prognosis. Mounting evidence suggests that lncRNAs can be used as predictive markers and therapeutic targets in the right context. In this study, we determined the role of lncRNA-PVT1 in GAC along with the value of inhibition of PVT1 using antisense oligos (ASOs). RNA scope in situ hybridization was used to analyze PVT1 expression in tumor tissue microarrays (TMAs) of GAC and paired normal tissues from 792 patients. Functional experiments, including colony formation and invasion assays, were performed to evaluate the effects of PVT1 ASO inhibition of PVT1 in vitro; patient-derived xenograft models were used to evaluate the anti-tumor effects of PVT1 ASOs in vivo. LncRNA-PVT1 was upregulated in GACs compared to the matched adjacent normal tissues in the TMA. LncRNA PVT1 expression was positively correlated with larger tumor size, deeper wall invasion, lymph node metastases, and short survival duration. Inhibition of PVT1 using PVT1 ASOs significantly suppressed tumor cell growth and invasion in vitro and in vivo. PVT1 expression was highly associated with poor prognosis in GAC patients and targeting PVT1 using PVT1 ASOs was effective at curtailing tumor cell growth in vitro and in vivo. Thus, PVT1 is a poor prognosticator as well as therapeutic target. Targeting PVT1 using PVT1 ASOs provides a novel therapeutic strategy for GAC.