Small nucleolar RNA ACA11 promotes proliferation, migration and invasion in hepatocellular carcinoma by targeting the PI3K/AKT signaling pathway
Small nucleolar RNA ACA11 promotes proliferation, migration and invasion in hepatocellular carcinoma by targeting the PI3K/AKT signaling pathway
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小核仁RNA ACA11通过靶向PI3K/AKT信号通路促进肝细胞癌的增殖、迁移和侵袭
DOI：
10.1016/j.biopha.2017.04.014
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发表时间：
2017-06-01
影响因子：
7.5
通讯作者：
Yuan, Yufeng
中科院分区：
文献类型：
--
作者：
Wu, Long;Zheng, Junying;Yuan, Yufeng
新出现的证据表明，肿瘤发生涉及小核仁RNA（snoRNA）的失调。然而，核仁小RNA ACA 11（ACA 11）在肝细胞癌（HCC）发生发展中的作用仍不清楚。采用定量RT-PCR检测92例HCC标本和7株HCC细胞系中ACA 11的表达。我们发现，ACA 11的表达显着上调，在肝癌组织和肝癌细胞系。HCC肿瘤中ACA 11的上调与组织学分级、HBV感染、巴塞罗那临床肝癌分期、门静脉癌栓和较差的患者生存率显著相关。ACA 11基因的敲除可诱导HCCLM 9和SK-Hep 1细胞发生G 0/G1期阻滞，并抑制其增殖、迁移和侵袭能力。在动物模型中，低ACA 11表达导致HCC生长减少。相反，ACA 11的转基因表达在体外和体内诱导Huh 7细胞的S期进展并增强其增殖、迁移和侵袭。最后，我们发现ACA 11通过激活PI 3 K/AKT通路促进细胞生长、迁移和侵袭，随后增加cyclinD 1表达并诱导EMT。这些结果表明，ACA 11在HCC中具有致癌作用，并且可能作为HCC患者的有希望的预后生物标志物和治疗靶点。(C)2017 Elsevier Masson SAS。All rights reserved.
Emerging evidence suggests that tumorigenesis involves dysregulation of small nucleolar RNAs (snoRNAs). However, the role of small nucleolar RNA ACA11 (ACA11) in the development of hepatocellular carcinoma (HCC) remains unknown. Expression of ACA11 was measured using quantitative RT-PCR in 92 HCC specimens and 7 HCC cell lines. We found that ACA11 expression was significantly upregulated in HCC tissues and hepatoma cell lines. This upregulation of ACA11 in HCC tumors was significantly associated with histological grade, HBV infection, Barcelona Clinic Liver Cancer stage, portal vein tumor thrombus and poorer patient survival. Knockdown of ACA11 induced G0/G1 phase arrest and suppressed proliferation, migration and invasion of HCCLM9 and SK-Hep1 cells. Low ACA11 expression resulted in decreased HCC growth in an animal model. Conversely, transgenic expression of ACA11 induced S phase progression and enhanced proliferation, migration and invasion of Huh7 cells in vitro and in vivo. Finally, we found that ACA11 promoted cell growth, migration and invasion through activation of the PI3K/AKT pathway, subsequently increasing cyclinD1 expression and inducing EMT. These results suggest that ACA11 has an oncogenic role in HCC and may serve as a promising prognostic biomarker and therapeutic target for patients with HCC. (C) 2017 Elsevier Masson SAS. All rights reserved.