High-throughput screening of Sirtuin family of genes in breast cancer

İğci, Mehri; Kalender, Mehmet; Borazan, Ersin; Bozgeyik, İbrahim; Bayraktar, Recep; Bozgeyik, Esra; Camcı, Celaletdin; Arslan, Ahmet

doi:10.1016/j.gene.2016.04.023

Cited by 51 publications

(45 citation statements)

References 35 publications

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“…However, no significant change in SIRT5 expression was observed in basal cell carcinoma tissues relative to non-cancerous tissues (12). For breast cancer, a previous study reported significantly elevated expression levels of SIRT5 in breast cancer tissues (14). Nevertheless, in the Oncomine database analysis conducted in the present study, the findings were inconsistent, with either higher or lower expression levels of SIRT5 observed in the breast tumor tissues of different datasets when compared with normal breast tissues.…”

Section: Discussioncontrasting

confidence: 81%

“…In recent years, studies have evaluated the potential roles of SIRTs in different cancer types (8)(9)(10). In particular, the expression of SIRT5 has been assessed in various types of cancer, including endometrial carcinoma, head and neck squamous cell carcinoma, basal cell carcinoma, lung and breast cancer (11)(12)(13)(14). However, to the best of our knowledge, no study has investigated the value of SIRT5 in predicting the pCR of TNBC patients to NAC, or the potential association of SIRT5 expression with the clinicopathological characteristics and prognosis of breast cancer patients.…”

Section: Sirt5 As a Biomarker For Response To Anthracycline-taxane-bamentioning

confidence: 99%

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SIRT5 as a biomarker for response to anthracycline-taxane-based neoadjuvant chemotherapy in triple-negative breast cancer

Che

Song

et al. 2018

Oncol Rep

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Neoadjuvant chemotherapy (NAC) is of great importance for patients with triple-negative breast cancer (TNBC) and the achievement of pathological complete response (pCR) to NAC in TNBC patients indicates survival benefits. However, the identification of reliable predictive biomarkers of pCR to NAC in TNBC patients remains an urgent and largely unattended medical issue. In the present study, we evaluated the differentially expressed genes (DEGs) between pCR and non-pCR patients after doxorubicin/cyclophosphamide therapy, followed by paclitaxel pre-operative treatment in 64 TNBC patients recorded in the GSE41998 dataset of Gene Expression Omnibus and identified 118 DEGs. Subsequently, we selected five core genes that were closely associated with the pCR of TNBC patients by using a genetic algorithm‑support vector machine-based method. Sirtuin 5 (SIRT5) was one of the five core genes and patients who achieved pCR expressed higher levels of SIRT5. Thus, we speculated that SIRT5 may be a potential predictive marker of the response to anthracycline-taxane-based chemotherapy. Oncomine analysis revealed that the expression levels of SIRT5 were higher in epirubicin/cyclophosphamide-docetaxel responders compared with non-responders. Furthermore, Gene Ontology analysis indicated that SIRT5 may affect the response to anthracycline-taxane-based chemotherapy by regulating the Rho pathway. It was also observed that SIRT5 was upregulated in TNBC and breast cancer with BRCA1 mutation subtypes. High SIRT5 expression was also associated with poor clinical outcomes of breast cancer patients. In conclusion, the present study revealed SIRT5 as a biomarker for response to anthracycline-taxane-based NAC in patients with TNBC and identified a series of novel biological functions of SIRT5 in breast cancer.

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Section: Discussioncontrasting

confidence: 81%

Section: Sirt5 As a Biomarker For Response To Anthracycline-taxane-bamentioning

confidence: 99%

SIRT5 as a biomarker for response to anthracycline-taxane-based neoadjuvant chemotherapy in triple-negative breast cancer

Che

Song

et al. 2018

Oncol Rep

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“…Several studies have investigated SIRT1 expression in breast cancer, but while some studies found upregulated SIRT1 expression, others did not concur. There are multiple reasons that could explain this discrepancy between studies: the fact that SIRT1 expression was evaluated only at transcriptional level [ 25 ], or using only breast cancer cell lines [ 26 , 27 ], and/or using human breast tissue samples but without accounting for the various molecular subtypes [ 25 , 28 – 30 ] or without having a statistically sufficient sample size [ 28 , 31 ]. This unclear picture promoted us to conduct the study here.…”

Section: Discussionmentioning

confidence: 99%

Dual SIRT1 expression patterns strongly suggests its bivalent role in human breast cancer

et al. 2017

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Breast cancer is the most common cancer in women, and the leading cause of cancer death in women worldwide. SIRT1 (silent mating type information regulation 2 homolog) 1 is a class-III histone deacetylase involved in apoptosis regulation, DNA repair and tumorigenesis. However, its role in breast carcinoma remains controversial, as both tumor-suppressive and tumor-promoting functions have been reported. Also, there are very few reports available where expression of SIRT1 is comprehensively analyzed in breast tumors classified by molecular subtype. Here, using a cohort of 50 human breast tumors and their matched normal tissues, we investigated SIRT1 expression levels in the 5 molecular subtypes of breast cancer according to the St Gallen classification (2013). Tumors and their corresponding normal tissue samples were collected from all patients, and SIRT1 mRNA and protein expression levels were then examined by real-time quantitative polymerase chain reaction and immunoblotting, respectively. After statistical analysis, the results showed a dual expression profile of SIRT1 in human breast carcinoma, with significant overexpression in luminal and HER2-enriched subtypes and significantly reduced expression in the triple-negative subtype. We also found an inverse correlation between SIRT1 expression and breast cancer aggressivity. These novel findings suggest that SIRT1 plays a dual role in breast tumors depending on its expression rate and the molecular subtype of the cancer. Our data also point to a potential role for SIRT1 as a prognostic biomarker in breast cancer.

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“…Breast cancer is the most frequent cancer among women, and ranks as the fifth cause of cancer death worldwide (13). Sirtuin family of genes shows differential expressions in breast cancer cells, which is often different from the expression in the breast cancer tissues (14). Since breast cancer cells have strikingly reduced Sirt3 level, and even 20% of them have almost no detectable Sirt3 protein (15), we wanted to examine the effect of de novo Sirt3 expression upon hyperoxic treatment in human MCF-7 breast cancer cells model.…”

Section: Introductionmentioning

confidence: 99%

De novo expression of transfected sirtuin 3 enhances susceptibility of human MCF-7 breast cancer cells to hyperoxia treatment

Pinterić

Podgorski

Sobočanec

et al. 2018

Free Radical Research

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Sirtuin 3 (Sirt3) has a promising role in cancer tumourigenesis and treatment, but there have been controversies about its role as oncogene or tumour suppressor in different types of cancer. Changes in its expression are associated with the excessive production of reactive oxygen species (ROS), thus contributing to mitochondrial dysfunction and age-related pathologies. Hyperoxic treatment (i.e. generator of ROS) was shown to support some tumourigenic properties, but finally suppresses growth of certain mammary carcinoma cells. Due to strikingly reduced Sirt3 level in many breast cancer cell lines, we aimed to clarify the effect of de novo Sirt3 expression upon hyperoxic treatment in the human MCF-7 breast cancer cells. De novo expression of Sirt3 decreased metabolic activity and cellular growth of MCF-7 cells, reduced expression of proangiogenic and epithelial mesenchymal transition genes, induced metabolic switch from glycolysis to oxidative phosphorylation, and decreased abundance of senescent cells. These effects were enhanced upon hyperoxic treatment: induction of DNA damage and upregulation of p53, with an increase of ROS levels followed by mitochondrial and antioxidant dysfunction, resulted in additional reduction of metabolic activity and inhibition of cellular growth and survival. The mitigation of tumorigenic properties and enhancement of the susceptibility of the MCF-7 breast cancer cells to the hyperoxic treatment upon de novo Sirt3 expression indicates that these factors, individually and in combination, should be further explored in vitro and particularly in vivo, as an adjuvant tumour therapy in breast cancer malignancies.

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High-throughput screening of Sirtuin family of genes in breast cancer

Cited by 51 publications

References 35 publications

SIRT5 as a biomarker for response to anthracycline-taxane-based neoadjuvant chemotherapy in triple-negative breast cancer

SIRT5 as a biomarker for response to anthracycline-taxane-based neoadjuvant chemotherapy in triple-negative breast cancer

Dual SIRT1 expression patterns strongly suggests its bivalent role in human breast cancer

De novo expression of transfected sirtuin 3 enhances susceptibility of human MCF-7 breast cancer cells to hyperoxia treatment

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