Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 90, Issue -, Pages 705-712Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2017.04.014
Keywords
Small nucleolar RNA; ACA11; Tumorigenesis; HCC; PI3K/AKT signaling pathway
Funding
- Hubei Province Health and Family Planning Scientific Research Project [WJ2017Z007]
- National Natural Science Foundation of China (NSFC) [81572450/H1617]
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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.
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