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

Oncology Reports
Junbin LiuJunhua Jin

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 prolife-ration 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 ...Continue Reading

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Mar 16, 2016·International Journal of Molecular Sciences·Ahmed S BayoumiIl-Man Kim
Dec 7, 2017·Frontiers in Microbiology·Hany S ZinadAndreas Werner
Sep 16, 2020·Journal of Experimental & Clinical Cancer Research : CR·Shanshan ZhaoSong Zhang
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Apr 1, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Eman A ToraihSomaya Hosny

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