The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma.

BACKGROUND:Dysfunctions of long non-coding RNA (lncRNAs) have been associated with the initiation and progression of hepatocellular carcinoma (HCC), but the clinicopathologic significance and potential role of lncRNA (pituitary tumor-transforming 3, pseudogene) in HCC remains largely unknown. METHODS:We compared the expression profiles of lncRNAs in 3 HCC tumor tissues and adjacent non-tumor tissues by microarrays. In situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to assess the level of duanyu1547G3P and prognostic values of duanyu1547G3P were assayed in two HCC cohorts (n = 46 and 90). Artificial modulation of duanyu1547G3P (down- and over-expression) was performed to explore the role of duanyu1547G3P in tumor growth and metastasis in vitro and in vivo. Involvement of (pituitary tumor-transforming 1), PI3K/AKT signaling and its downstream signals were validated by qRT-PCR and western blot. RESULTS:We found that duanyu1547G3P was frequently up-regulated in HCC and its level was positively correlated to tumor size, TNM stage and poor survival of patients with HCC. Enforced expression of duanyu1547G3P significantly promoted cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, duanyu1547G3P knockdown had opposite effects. Mechanistically, over-expression of duanyu1547G3P up-regulated activated PI3K/AKT signaling and its downstream signals including cell cycle progression, cell apoptosis and epithelial-mesenchymal transition (EMT)-associated genes. CONCLUSIONS:Our findings suggest that a valuable marker of HCC prognosis, promotes tumor growth and metastasis via up-regulating duanyu1547G1 and activating PI3K/AKT signaling in HCC and might represent a potential target for gene-based therapy.

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