Association of SIRT1 and HMGA1 expression in non-small cell lung cancer

Abstract

Abstract. The roles of Silent mating type information regulation 2 homolog 1 (SIRT1) and High mobility group A1 (HMGA1) in human diseases have been extensively studied separately; however, to the best of our knowledge, the current study is the first to report on their interrelationship in lung cancer. The association of SIRT1 and HMGA1 in non-small cell lung cancer (NSCLC) was investigated by evaluating their expression and prognostic significance in 260 patients with NSCLC using immunohistochemistry. SIRT1 and HMGA1 expression were found to be significantly correlated with each other (P<0.001), and both were significantly associated with clinicopathological parameters, including histological type and degree of differentiation. In squamous cell carcinoma (SCC), SIRT1 + specimens were significantly associated with shorter overall survival (OS) time (P=0.019). However, in patients with adenocarcinoma (AD), no association was identified between SIRT1 and OS. In addition, HMGA1 + specimens were significantly associated with poor differentiation (P=0.028), and were more frequent in SCC than AD (P=0.015). However, HMGA1 was not associated with OS on univariate Cox regression analysis or Kaplan-Meier analysis (both P>0.05). SIRT1/HMGA1 coexpression was significantly associated with male gender (P=0.016), and moderately and poorly differentiated histological grade (P=0.025). The findings indicate that SIRT1 and HMGA1 may have significant effects during tumor progression in NSCLC, particularly in patients with SCC, and are potentially useful as prognostic indicators for patients with NSCLC.

<em>SIRT1</em> gene polymorphisms and risk of lung cancer

“…In this study, we assessed whether genetic variations in SIRT1 are associated with NSCLC, which consists mainly of SCC and AD and accounts for nearly 80% of all lung cancer cases. According to our previous report, 39 the expression of SIRT1 was significantly associated with unfavorable SCC characteristics, but not with AD characteristics; furthermore, we compared the SNP frequencies in SCC patients vs controls and AD patients vs controls. We investigated four TagSNPs: rs12778366 (C/T, lies in the 5′ upstream), rs3758391 (C/T, lies in the 5′ upstream), rs2273773 (C/T, lies in the coding) and rs4746720 (C/T, lies in the 3′ UTR), which could capture all the SNPs with minor allele frequency ≥0.05 across the SIRT1 gene region in 257 NSCLC patients (200 men and 57 women), 79 SCC patients (71 men and 8 women), 124 AD patients (77 men and 47 women) and 246 healthy controls (186 men and 60 women).…”

Ubiquitin-Specific Protease 22/Silent Information Regulator 1 Axis Plays a Pivotal Role in the Prognosis and 5-Fluorouracil Resistance in Hepatocellular Carcinoma

“…Silent information regulator 1 (SIRT1), a member of the sirtuin family of nicotinamide adenine dinucleotide (NAD +)-dependent class III histone deacetylases, controls a variety of biologic processes ranging from metabolic homeostasis, neurodegenerative diseases, aging and cancer [9]. Studies have demonstrated that SIRT1 localizes predominantly to the nucleus, and its expression is increased in colorectal [10], ovarian [11] and lung cancers [12]. Xiong et al [13] demonstrated that SIRT1 is overexpressed in HCC and plays an oncogenic role in HCC by enhancing cell proliferation and resistance to chemotherapy.…”

HMGA1 Overexpression is Associated With the Malignant Status and Progression of Breast Cancer

“…High mobility group A1 (HMGA1), a member of the HMGA family, is highly expressed during embryogenesis (Pegoraro et al, ), while HMGA1 protein expression levels are low or undetectable in normal adult tissues (Zhou et al, ; van't Veer et al, ). Studies have shown that HMGA1 plays an important role in several types of cancers, such as breast cancer (Cianfrocca et al, ), colorectal cancer (Williama et al, ), pancreatic cancer (Piscuoglio et al, ), prostate cancer (Zhang et al, ), ovarian cancer (Liu et al, ), and lung cancer (Lin et al, ). Furthermore, some studies have reported that HMGA1 is highly expressed in human breast cancer tissues, and the overexpression of HMGA1 is associated with breast cancer progression (Huang et al, ).…”