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

Abstract

BackgroundDysfunctions 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 PTTG3P (pituitary tumor-transforming 3, pseudogene) in HCC remains largely unknown.MethodsWe 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 PTTG3P and prognostic values of PTTG3P were assayed in two HCC cohorts (n = 46 and 90). Artificial modulation of PTTG3P (down- and over-expression) was performed to explore the role of PTTG3P in tumor growth and metastasis in vitro and in vivo. Involvement of PTTG1 (pituitary tumor-transforming 1), PI3K/AKT signaling and its downstream signals were validated by qRT-PCR and western blot.ResultsWe found that PTTG3P 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 PTTG3P significantly promoted cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, PTTG3P knockdown had opposite effects. Mechanistically, over-expression of PTTG3P up-regulated PTTG1, activated PI3K/AKT signaling and its downstream signals including cell cycle progression, cell apoptosis and epithelial-mesenchymal transition (EMT)-associated genes.ConclusionsOur findings suggest that PTTG3P, a valuable marker of HCC prognosis, promotes tumor growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in HCC and might represent a potential target for gene-based therapy.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0841-x) contains supplementary material, which is available to authorized users.

The Emerging Role of Long Non-Coding RNAs in the Metastasis of Hepatocellular Carcinoma

“…For example, the lncRNA TSLNC8 and lncRNA-ATB mentioned above are related to the STAT3 pathway. LncRNA PTTG3P (pituitary tumor-transforming 3, pseudogene) promotes the growth and metastasis of HCC by up-regulating PTTG1 and activating PI3K/AKT signaling [65]. The lncRNA-AWPPH linc-GALH, which can promote the metastasis of HCC, is also involved in the regulation of AKT signaling pathway [18,35].…”

<p>LINC02476 Promotes the Malignant Phenotype of Hepatocellular Carcinoma by Sponging miR-497 and Increasing HMGA2 Expression</p>

“…5 For instance, CRNDE, TUG1 and NEAT1 are three examples of lncRNAs that are often elevated in HCC and are related to worse prognoses. [6][7][8] MicroRNAs (miRNAs) are a family of small noncoding RNAs 9 that post-transcriptionally control mRNAs by binding to their 3ʹ untranslated regions (UTRs) leading to direct transcript degradation or translational repression. 10 It is estimated that miRNAs can modulate more than 70% of human genes.…”

Long noncoding RNA TP53TG1 promotes pancreatic ductal adenocarcinoma development by acting as a molecular sponge of microRNA‐96

“…Although only a small portion of lncRNAs have been characterized in detail, many lncRNAs have emerged as regulators of various biological processes, such as epigenetic regulation, alternative splicing, RNA decay, cell cycle control, and cell fate determination . Furthermore, multiple lines of evidence suggest that the abnormal expression of lncRNAs is associated with the development of diverse human diseases, and specific lncRNAs have also been shown to play a critical role in tumor initiation and progression, including PDAC . For example, LINC00673 is able to promote protein tyrosine phosphatase PTPN11 degradation through ubiquitination, resulting in decreased proliferation of pancreatic cancer cells .…”