A Positive Feedback Regulation Involving PVT1 and HER2/hER3 Promotes Progression of High-grade Serous Ovarian Cancer

Abstract Background In recent years, long noncoding RNAs (lncRNAs) have been reported frequently to play important roles in specific cancers, including high-grade serous ovarian cancer (HGSOC). PVT1 is an important oncogenic lncRNA highly expressed in various cancers. However, little is known about the role of PVT1 in HGSOC and underlying mechanisms. Methods The expression levels of PVT1 and HER2/3 in HGSOC tissue and adjacent normal tissue were determined by qRT-PCR. MTT and transwell assays were used to identify the effects of PVT1 cell proliferation and migration respectively. Dual-luciferase reporter assay and RIP experiment were carried out to verify target genes of PVT1. ChIP experiment was used to identify that HER2 was transcription factor of PVT1. Results Our results showed that PVT1 expression was up-regulation in human HGSOC specimens and promoted ovarian cancer cell proliferation and migration. We further validated that HER2 was a direct transcription factor for facilitating PVT1 expression. In return, PVT1 enhanced HER2 transcript stability. Moreover, bioinformatics analysis and dual luciferase reporter assay results uncovered that PVT1 functioned as a competing endogenous RNA (ceRNA) for miR-1301-3p to promote cell proliferation and migration by increasing HER3 expression. Conclusions Taken together, our results showed that PVT1, controlled by HER2, elevated HER2 and HER3 expression to promote HGSOC progression. Thus, PVT1 can be regarded as a vital diagnostic biomarker for HGSOC and a potential novel therapeutic target.