Abstract
BackgroundEmerging 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.MethodsThe 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.ResultsSNORD113-1 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.ConclusionsSNORD113-1 functions as a tumor suppressor role in HCC and may be important as a potential diagnostic and therapeutic target for HCC.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-216) contains supplementary material, which is available to authorized users.
Highlights
Emerging evidence suggests that small nucleolar RNAs are involved in tumorigenesis
The four most upregulated genes were pepsinogen C (PGC), alpha fetoprotein (AFP), aldoketo reductase family 1 member B10 (AKR1B10) and glypican 3 (GPC3), which showed greater than 30-fold higher expression in hepatocellular carcinoma (HCC) tumors than adjacent non-tumor tissues
AFP is the only serum biomarker that has widely been used in the diagnosis of HCC [11]; GPC3 is a potential reliable biomarker and therapeutic target in HCC [12]; PGC is overexpressed in HCC [13]; AKR1B10 is a valuable novel biomarker candidate for staging of HCC [14]
Summary
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. An increasing number of studies investigating the role of non-coding RNAs (ncRNAs) in the pathology of HCC have been reported, including microRNAs (miRNAs), long non-coding RNA (lncRNAs) and small nucleolar RNAs (snoRNAs) [3,4,5]. SnoRNAs belong to a group of ncRNA molecules of that are in the range of 60–300 nucleotides in length. This group of ncRNAs is predominantly found in the nucleolus and functions to guide RNAs for posttranscriptional modification of ribosomal RNAs and some spliceosomal RNAs [6]. Accumulating evidence suggests that snoRNAs may be actively involved in carcinogenesis and play diverse roles in tumor biology
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