Abstract
BackgroundEmerging evidence indicates that Long non-coding RNAs (LncRNAs) and microRNAs (miRNAs) play crucial roles in tumor progression, including hepatocellular carcinoma (HCC). However, whether there is a crosstalk between LncRNA pituitary tumor-transforming 3 (PTTG3P) and miR-383 in HCC remains unknown. This study is designed to explore the underlying mechanism by which LncRNA PTTG3P sponges miR-383 during HCC progression.MethodsqPCR and Western blot were used to analyze LncRNA PTTG3P, miR-383 and other target genes’ expression. CCK-8 assay was performed to examine cell proliferation. Annexin V-PE/PI and PI staining were used to analyze cell apoptosis and cell cycle distribution by flow cytometry, respectively. Transwell migration and invasion assays were used to examine cell migration and invasion abilities. An in vivo xenograft study was performed to detect tumor growth. Luciferase reporter assay and RNA pull-down assay were carried out to detect the interaction between miR-383 and LncRNA PTTG3P. RIP was carried out to detect whether PTTG3P and miR-383 were enriched in Ago2-immunoprecipitated complex.ResultsIn this study, we found that PTTG3P was up-regulated in HCC tissues and cells. Functional experiments demonstrated that knockdown of PTTG3P inhibited cell proliferation, migration and invasion, and promoted cell apoptosis, acting as an oncogene. Mechanistically, PTTG3P upregulated the expression of miR-383 targets Cyclin D1 (CCND1) and poly ADP-ribose polymerase 2 (PARP2) by sponging miR-383, acting as a competing endogenous RNA (ceRNA). The PTTG3P-miR-383-CCND1/PARP2 axis modulated HCC phenotypes. Moreover, PTTG3P also affected the PI3K/Akt signaling pathway.ConclusionThe data indicate a novel PTTG3P-miR-383-CCND1/PARP2 axis in HCC tumorigenesis, suggesting that PTTG3P may be used as a potential therapeutic target in HCC.Graphical
Highlights
Emerging evidence indicates that Long non-coding RNAs (LncRNAs) and microRNAs play crucial roles in tumor progression, including hepatocellular carcinoma (HCC)
Pituitary tumor-transforming 3 (PTTG3P) is highly expressed in HCC tissues and cell lines Firstly, we analyzed the profiles of HCC patients from the Gene Expression Omnibus (GEO) (GSE 76427 and GSE 84402 dataset), and found that PTTG3P was upregulated in HCC tissues compared to adjacent nontumor tissues
Knockdown of PTTG3P inhibits cell migration and invasion Considering that metastasis is an important factor involved in tumor progression, we aimed to investigate the effect of PTTG3P on cell migration and invasion
Summary
Emerging evidence indicates that Long non-coding RNAs (LncRNAs) and microRNAs (miRNAs) play crucial roles in tumor progression, including hepatocellular carcinoma (HCC). Despite a variety of advanced therapeutic approaches, including liver resection, chemotherapy, and radiotherapy, or molecular targeted therapy, the prognosis of some HCC is still poor. Accumulating evidence indicates that lncRNAs, longer than 200 nucleotides in length and no protein coding potentials, exert crucial roles in pathological process, including cancer development and progression [7, 8]. The pseudogene-derived lncRNA PTTG3P has been reported to act as an oncogene in gastric cancer [20] and HCC [21], but the molecular mechanism how PTTG3P interacts with miRNAs in HCC remains poor
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