A novel mutation in SIRT1-AS leading to a decreased risk of HCC

  • Authors:
    • Junbin Liu
    • Weihong Wu
    • Junhua Jin
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  • Published online on: August 19, 2015     https://doi.org/10.3892/or.2015.4205
  • Pages: 2343-2350
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Abstract

Natural antisense transcripts (NATs) have recently been associated with the development of human cancers. However, the interrelationship between NATs and their sense transcripts in hepatocellular carcinoma (HCC) has not been well-characterized. The aim of the present study was to characterize the AS lncRNA SIRT1-AS, which suppressed the miRNA-induced translational repression of SIRT1 mRNA by masking the miR-29c binding site on the SIRT1 3'UTR. A 763-nucleotide (nt), single-exon NAT transcribed from the antisense strand of SIRT1 gene, designated as SIRT1-AS, was identified using strand-specific RT-PCR and northern blot analyses. SIRT1-AS overexpression promoted the prolife­ration of the human HCC cell lines by upregulating the SIRT1 protein level. The mechanism was that SIRT1-AS bound to SIRT1 mRNA at 3'UTR, masked the miR-29c binding site and stabilized SIRT1 mRNA. A single-nucleotide mutation (622U>C) in the SIRT1-AS sequence was found when we used gene sequencing as an assistant approach for HCC diagnosis. Bioinformatics and the RNase protection assay revealed that the mutation led to a marked alteration in the secondary structure of SIRT1-AS and caused its inability to bind with SIRT1 mRNA. Overexpression of this mutant did not have a promoting effect on HCC cell proliferation. Moreover, the mean level of SIRT1-AS was much higher in the HCC patients compared to non-hepatopathy volunteers (P<0.01), whereas the opposite effect was observed for the mutant ratio. The odds ratio (OR) analysis also suggested the 622C mutation reduced the risk of HCC. Taken together, we identified a novel mutation in SIRT1-AS leading to a decreased risk of HCC. The results of the present study suggest that the 622C mutant of SIRT1 antisense transcript suppresses HCC cell line proliferation, decreases the risk of HCC and is a potential target for gene therapy.
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November-2015
Volume 34 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Liu J, Wu W and Jin J: A novel mutation in SIRT1-AS leading to a decreased risk of HCC. Oncol Rep 34: 2343-2350, 2015
APA
Liu, J., Wu, W., & Jin, J. (2015). A novel mutation in SIRT1-AS leading to a decreased risk of HCC. Oncology Reports, 34, 2343-2350. https://doi.org/10.3892/or.2015.4205
MLA
Liu, J., Wu, W., Jin, J."A novel mutation in SIRT1-AS leading to a decreased risk of HCC". Oncology Reports 34.5 (2015): 2343-2350.
Chicago
Liu, J., Wu, W., Jin, J."A novel mutation in SIRT1-AS leading to a decreased risk of HCC". Oncology Reports 34, no. 5 (2015): 2343-2350. https://doi.org/10.3892/or.2015.4205