The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma.
The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma.
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DOI：
10.1186/s12943-018-0841-x
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发表时间：
2018-05-26
期刊：
影响因子：
37.3
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Huang JL;Cao SW;Ou QS;Yang B;Zheng SH;Tang J;Chen J;Hu YW;Zheng L;Wang Q
长链非编码RNA（lncRNA）的功能障碍与肝细胞癌（HCC）的发生和进展有关，但lncRNA PTTG3P（垂体肿瘤转化3，假基因）在HCC中的临床病理意义和潜在作用仍然很大程度上未知。我们通过微阵列比较了 3 个 HCC 肿瘤组织和癌旁非肿瘤组织中 lncRNA 的表达谱。应用原位杂交 (ISH) 和定量实时聚合酶链反应 (qRT-PCR) 评估 PTTG3P 水平，并在两个 HCC 队列（n = 46 和 90）中测定 PTTG3P 的预后价值。对PTTG3P（下调和过度表达）进行人工调节，以探索PTTG3P在体外和体内肿瘤生长和转移中的作用。通过 qRT-PCR 和蛋白质印迹验证了 PTTG1（垂体肿瘤转化 1）、PI3K/AKT 信号及其下游信号的参与。我们发现PTTG3P在HCC中频繁上调，其水平与肿瘤大小、TNM分期和HCC患者的不良生存率呈正相关。 PTTG3P的强制表达显着促进体外细胞增殖、迁移和侵袭，以及体内肿瘤发生和转移。相反，PTTG3P 敲低则产生相反的效果。从机制上讲，PTTG3P的过度表达上调PTTG1，激活PI3K/AKT信号及其下游信号，包括细胞周期进程、细胞凋亡和上皮间质转化（EMT）相关基因。我们的研究结果表明，PTTG3P 是 HCC 预后的一个有价值的标志物，通过上调 PTTG1 并激活 HCC 中的 PI3K/AKT 信号传导来促进肿瘤生长和转移，并且可能代表基因治疗的潜在靶点。本文的在线版本 (10.1186/s12943-018-0841-x) 包含补充材料，可供授权用户使用。
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 PTTG3P (pituitary tumor-transforming 3, pseudogene) in HCC remains largely unknown. 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 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. We 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. Our 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. The online version of this article (10.1186/s12943-018-0841-x) contains supplementary material, which is available to authorized users.
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影响因子：
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作者：
Cao SW;Huang JL;Chen J;Hu YW;Hu XM;Ren TY;Zheng SH;Lin JD;Tang J;Zheng L;Wang Q
通讯作者：
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