Expression and role of SIRT1 in hepatocellular carcinoma

Abstract

Abstract. silent mating type information regulation 2 homolog 1 (sIrt1) is a multifaceted, nicotinamide adenine dinucleotide-dependent protein deacetylase with involvement in a wide variety of cellular processes ranging from cancer to aging. expression of sIrt1 was evaluated in 90 cases of hepatocellular carcinoma (HCC) and five HCC cell lines. The relationship between the mutation status of p53 and expression of sIrt1 was also investigated in 10 fresh HCC tissues. synthetic small interfering rNA was used to silence sIrt1 gene expression by rNA interference (rNAi), and cell growth and cell cycle progression were assessed. expression of sIrt1 was significantly elevated in the HCC tissues when compared to that of non-tumor tissues (p<0.001). Overexpression of sIrt1 and p53 was observed in 56% (50 of 90) and in 30% (27 of 90) of the HCCs, respectively. expression of sIrt1 showed significant correlation with gender (p=0.023), serum AFP levels (p=0.030), viral infection (p=0.005) and p53 expression (p<0.021). Western blot analysis found no correlation between p53 mutation and expression levels of sIrt1. sIrt1 silencing was found to induce cell growth arrest in HCC cells. these results suggest an association of sIrt1 expression with HCC development and that sIrt1 plays a role in cancer cell growth.

DNA Methyltransferases 1 and 3b Expression in Huh-7 Cells Expressing HCV Core Protein of Different Genotypes

“…It is already known that SIRT1 protein cooperates with DNMTs to repress transcription [33] and relevant chemotherapeutic drugs have already been tested in combination with DNMT inhibitors, HDAC inhibitors, and sirtuin inhibitors [32]. Moreover, SIRT1-silencing sensitized HCC cells to doxorubicin treatment [22]. A signaling cross talk between SIRT1 and STAT3 has been shown in the liver; STAT3 phosphorylation and function were found to be regulated by the nutritional status in mice, through SIRT1-mediated deacetylation of key STAT3 lysine residues.…”

“…We and others have suggested a function of SIRT1 in HCC development [13,21,22]. In order to examine whether SIRT1 has a role in the modulation of DNMT1 and 3b expression induced by HCV core protein, we incubated Huh-7 cells expressing HCV core 1b with a SIRT1 inhibitor, sirtinol, to evaluate DNMTs expression.…”

Potentiation of the anticancer effects of everolimus using a dual mTORC1/2 inhibitor in hepatocellular carcinoma cells

“…SIRT1 is expressed in human HCC carcinoma tissues at a higher level than in adjacent nontumor liver tissues [43]. Furthermore, it was reported that patients with SIRT1-positive HCC have a lower 10-year survival rate than those with SIRT1-negative HCC [42, 44]. The downstream targets of SIRT1 include p53 [45, 46], telomerase [43], YAP (Yes-associated protein) [47], and PTEN/PI3K/Akt [48, 49] signaling, all of which can promote HCC progression.…”

SIRT1 deacetylase is overexpressed in human melanoma and its small molecule inhibition imparts anti-proliferative response via p53 activation

“…However, its expression status in melanoma is poorly defined and in need of further investigation. In cancers which overexpress SIRT1, inhibition through small molecule inhibitors or genetic knockdown leads to an induction of cell cycle arrest and/or apoptosis [9–14]. In breast cancer and chronic myeloid leukemia, this effect was shown to be accompanied by increased acetylation of the tumor suppressor p53 [11, 12].…”