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Published on: April 25, 2018
Small nucleolar RNA 113-1 suppresses tumorigenesis in hepatocellular carcinoma
Gang Xu, Fang Yang, Cui-Ling Ding
1Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, 800 XiangYin RD, Shanghai 200433, China. wonwin29@126.com.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
SNORD113-1 functions as a tumor suppressor role in HCC and may be important as a potential diagnostic and therapeutic target for HCC.
Insights
Small nucleolar RNA 113-1 (SNORD113-1) is downregulated in hepatocellular carcinoma (HCC), suppressing tumor growth. This suggests SNORD113-1 may serve as a diagnostic and therapeutic target for HCC.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Small nucleolar RNAs (snoRNAs) are increasingly implicated in cancer development.
- The specific role of small nucleolar RNA 113-1 (SNORD113-1) in hepatocellular carcinoma (HCC) pathogenesis was previously uncharacterized.
Purpose of the Study:
- To investigate the expression patterns of SNORD113-1 in HCC.
- To elucidate the functional role of SNORD113-1 in HCC tumorigenesis.
- To explore the potential of SNORD113-1 as a diagnostic or therapeutic target for HCC.
Main Methods:
- Quantitative RT-PCR was used to measure SNORD113-1 expression in 112 HCC tissues and paired non-tumor tissues.
- In vitro (HepG2, Huh7 cells) and in vivo (xenograft nude mouse model) experiments assessed the impact of SNORD113-1 on HCC progression.
- Sodium bisulfite sequencing identified CpG methylation in the SNORD113-1 promoter region.
- Cancer pathway reporters were utilized to investigate the underlying molecular mechanisms.
Main Results:
- SNORD113-1 expression was significantly reduced in HCC tumors compared to adjacent non-tumor tissues.
- Lower SNORD113-1 levels correlated with poorer patient survival.
- Increased CpG methylation was observed in the SNORD113-1 promoter in HCC tissues.
- SNORD113-1 demonstrated tumor-suppressive effects by inhibiting cancer cell proliferation in vitro and in vivo.
- SNORD113-1 inactivated ERK1/2 and SMAD2/3 phosphorylation, impacting MAPK/ERK and TGF-β signaling pathways.
Conclusions:
- SNORD113-1 acts as a tumor suppressor in hepatocellular carcinoma.
- SNORD113-1 warrants further investigation as a potential biomarker for HCC diagnosis and a therapeutic target for HCC treatment.
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