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Up-regulation of small nucleolar RNA 78 is correlated with aggressive phenotype and poor prognosis of hepatocellular carcinoma

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Tumor Biology

Abstract

Small nucleolar RNAs (snoRNAs) as a novel molecular species may have significant and comprehensive influences on the development and progression of hepatocellular carcinoma (HCC). We recently characterized snoRNA transcriptome signatures in HCC tissues by small RNA sequencing and found that small nucleolar RNA 78 (SNORD78) was associated with HCC. However, little is known about the pathological role of SNORD78 in HCC patients. This study aimed to profile SNORD78 expression signature and then to explore the pathogenesis of SNORD78 in HCC. The real-time PCR results showed that SNORD78 was greatly upregulated in HCC tissues than adjacent noncancerous tissues (p = 0.004). Correlation analysis showed that high-level expression of SNORD78 was notably associated with tumor number (single vs. multiply, p = 0.02), stage (I∼II vs. III∼IV, p = 0.014), and distant metastasis (absent vs. present, p = 0.01) in HCC patients. Univatiate and multivariate analyses showed that SNORD78 was a significant prognostic predictor for overall survival and recurrence-free survival of HCC patients (hazard ratio = 1.375, 95 % CI = 1.125–1.680, p = 0.002; hazard ratio = 1.418, 95 % CI = 1.201–1.675, p < 0.001). Moreover, Kaplan-Meier analysis showed that high-level expression of SNORD78 was associated with short overall survival and recurrence-free survival of HCC patients (p = 0.023, 0.014). Functionally, knockdown of SNORD78 significantly inhibited cellular proliferation, migration, and invasion of SK-Hep-1 via inducing G0/G1 cell cycle arrest and apoptosis. In conclusion, SNORD78 may be associated with aggressive phenotype and poor prognosis of HCC.

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Acknowledgments

This study was funded by the National Basic Research Program of China (973 Program) (2012CB720600, 2012CB720605).

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Authors and Affiliations

  1. Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China

    Pei Ma, Lu Han, Wei Jing & Xin Zhou

  2. Department of Hepatobiliary and Pancreas, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China

    Haitao Wang & Zhisu Liu

Authors
  1. Pei Ma
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  2. Haitao Wang
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  3. Lu Han
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  4. Wei Jing
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  5. Xin Zhou
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  6. Zhisu Liu
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Corresponding authors

Correspondence to Xin Zhou or Zhisu Liu.

Ethics declarations

The study was approved by the medical ethical committee of Zhongnan Hospital of Wuhan University. All participants were Han population from China, who gave their informed written consent.

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None

Additional information

Pei Ma and Haitao Wang contributed equally to the work and should be considered as first authors.

Electronic supplementary material

Supplementary Fig. 1

Sequencing and amplification of SNORD78 (a) sequence of SNORD78 RT-PCR products by clone sequencing and (b) amplification of series of diluted SNORD78 products by RT-PCR assay (GIF 55 kb)

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Ma, P., Wang, H., Han, L. et al. Up-regulation of small nucleolar RNA 78 is correlated with aggressive phenotype and poor prognosis of hepatocellular carcinoma. Tumor Biol. 37, 15753–15761 (2016). https://doi.org/10.1007/s13277-016-5366-6

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  • DOI: https://doi.org/10.1007/s13277-016-5366-6

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