Small nucleolar RNA 113-1 suppresses tumorigenesis in hepatocellular carcinoma.
Small nucleolar RNA 113-1 suppresses tumorigenesis in hepatocellular carcinoma.
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DOI：
10.1186/1476-4598-13-216
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发表时间：
2014-09-14
期刊：
影响因子：
37.3
通讯作者：
Qi ZT
中科院分区：
文献类型：
--
作者：
Xu G;Yang F;Ding CL;Zhao LJ;Ren H;Zhao P;Wang W;Qi ZT
新的证据表明，小核仁RNA(SnoRNAs)参与了肿瘤的发生。小核仁RNA113-1(SNORD113-1)在肝细胞癌发生发展中的作用尚不清楚。采用定量RT-PCR方法检测112例肝细胞癌组织中SNORD113-1的表达，并与配对的非肿瘤组织进行比较。研究了SNORD113-1在HepG2和Huh7细胞以及裸鼠移植瘤模型中对肝癌发生的影响。亚硫酸氢钠测序鉴定SNORD113-1基因启动子区域CpG甲基化。癌症途径记者研究SNORD113-1抑制肿瘤形成的机制。SNORD113-1在肝细胞癌组织中的表达较癌旁组织显著下调，且与患者的生存期显著相关。此外，肝癌组织中SNORD113-1基因启动子区CpG甲基化水平高于癌旁组织。在功能上，SNORD113-1抑制了HepG2和Huh7细胞以及裸鼠移植瘤模型中癌细胞的生长。此外，SNORD113-1还可抑制丝裂原活化蛋白激酶/ERK和转化生长因子-β途径中ERK1/2和Smad2/3的磷酸化。SNORD113-1在肝细胞癌中发挥肿瘤抑制作用，可能成为肝细胞癌潜在的诊断和治疗靶点。本文的在线版本(DOI：10.1186/1476-4598-13-216)包含补充材料，可供授权用户使用。
Emerging evidence suggests that small nucleolar RNAs (snoRNAs) are involved in tumorigenesis. The roles of small nucleolar RNA 113–1 (SNORD113-1) on the development of hepatocellular carcinoma (HCC) remain unknown. The expression of SNORD113-1 was measured in 112 HCC tumor tissues using quantitative RT-PCR and compared with expression levels from with paired non-tumor tissues. The effects of SNORD113-1 on HCC tumorigenesis were investigated in HepG2 and Huh7 cells as well as a xenograft nude mouse model. CpG methylation within the promoter region of the SNORD113-1 gene was identified using Sodium bisulfite sequencing. Cancer pathway reporter investigate the mechanism by which SNORD113-1 suppressed tumorigenesis. SNORD113-1 expression was significantly downregulated in HCC tumors compared with adjacent non-tumor tissues, and downregulation of SNORD113-1 in HCC tumors was significantly associated with worse survival of patients. In addition, CpG methylation at the promoter region of the SNORD113-1 gene was higher in HCC tumors than adjacent non-tumor tissues. Functionally, SNORD113-1 suppressed cancer cell growth in HepG2 and Huh7 cells and in a xenograft nude mouse model. Furthermore, SNORD113-1 inactivated the phosphorylation of ERK1/2 and SMAD2/3 in MAPK/ERK and TGF-β pathways. SNORD113-1 functions as a tumor suppressor role in HCC and may be important as a potential diagnostic and therapeutic target for HCC. The online version of this article (doi:10.1186/1476-4598-13-216) contains supplementary material, which is available to authorized users.
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