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Yi-Chao Hsu, Yu-Ting Wu, Chia-Ling Tsai, Yau-Huei Wei
In mammalian cells, there are seven members of the sirtuin protein family (SIRT1-7). SIRT1, SIRT6, and SIRT7 catalyze posttranslational modification of proteins in the nucleus, SIRT3, SIRT4, and SIRT5 are in the mitochondria and SIRT2 is in the cytosol. SIRT1 can deacetylate the transcription factor SOX2 and regulate induced pluripotent stem cells (iPSCs) reprogramming through the miR-34a-SIRT1-p53 axis. SIRT2 can regulate the function of pluripotent stem cells through GSK3β. SIRT3 can positively regulate PPAR gamma coactivator 1-alpha (PGC-1α) expression during the differentiation of stem cells...
March 2018: Experimental Biology and Medicine
Zhigang Deng, Xingbiao Wang, Xuan Long, Wanzhong Liu, Chunhua Xiang, Feng Bao, Dong Wang
Sirtuin 7 (Sirt7) is a member of the sirtuin protein family and is implicated in various carcinomas; however, the function of Sirt7 in colorectal carcinoma (CRC) remains unclear. The present study aimed to explore the biological function of Sirt7 in CRC tissues and cell lines, and to investigate the potential underlying mechanism by performing reverse transcription-quantitative polymerase chain reaction analyses, western blot analyses, luciferase reporter assays, cell proliferation and invasion assays. It was demonstrated that Sirt7 presented a higher expression in CRC tissues and cell lines compared with that in normal tissues and cells, and this higher expression was correlated with the tumor size, the tumor, node and metastasis stage and distant metastasis...
March 2018: Experimental and Therapeutic Medicine
Wenzhi Li, Zhe Sun, Chen Chen, Lin Wang, Zhimin Geng, Jie Tao
Accumulating evidence indicates that sirtuin7 (SIRT7) plays an oncogenic role in the main types of liver cancer, hepatocellular carcinoma (HCC). Nevertheless, the clinical significance of SIRT7 and its role in cholangiocarcinoma (CCA) is largely undiscovered. Here, we found that SIRT7 displayed higher expression in CCA tissues compared to intrahepatic normal bile duct and surrounding liver tissues based on The Cancer Genome Atlas (TCGA) data. Our data further confirmed that SIRT7 was overexpressed in CCA patient tissues and cell lines...
February 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Xiaoqian Zhou, Yidun Xie, Houan Xiao, Xudong Deng, Yu Wang, Liyuan Jiang, Chen Liu, Rui Zhou
MicroRNAs (miRNAs) play critical roles in various pathological processes, including hypertrophic scar (HS) formation. However, the precise role of miRNAs in HS formation remains largely unknown. In this study, we aimed to investigate the role of miR-519d in HS formation. We found that miR-519d expression was significantly downregulated in HS tissues and fibroblasts. Overexpression of miR-519d inhibited the expression of type I collagen (Col I), type III collagen (Col III) and α-smooth muscle actin (α-SMA) in HS fibroblasts...
February 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Kana Tanabe, Jiaan Liu, Daiki Kato, Hitoshi Kurumizaka, Kenzo Yamatsugu, Motomu Kanai, Shigehiro A Kawashima
Chromatin structure and gene expression are dynamically regulated by posttranslational modifications of histones. Recent advance in mass spectrometry has identified novel types of lysine acylations, such as butyrylation and malonylation, whose functions and regulations are likely different from those of acetylation. Sirtuins, nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, catalyze various deacylations. However, it is poorly understood how distinct sirtuins regulate the histone acylation states of nucleosomes that have many lysine residues...
February 8, 2018: Scientific Reports
Shengchao Li, Weiping Zheng
Sirtuins are a family of intracellular enzymes whose enzymatic activities include catalyzing the β-nicotinamide adenine dinucleotide (β-NAD+)-dependent Nɛ-acyl-lysine deacylation and the β-NAD+-dependent mono-ADP-ribosylation. Among the seven sirtuin family members (i.e., SIRT1-7) thus far identified in mammals including humans, we know SIRT1/2/3/5/6 better than SIRT4/7 as for their enzymatic activities and the cellular roles of the reactions they catalyze. This chapter will provide an updated account on the enzymology and biology of SIRT4 and SIRT7, the two less well-understood mammalian sirtuins...
2018: Progress in Molecular Biology and Translational Science
Wataru Korogi, Tatsuya Yoshizawa, Md Fazlul Karim, Hironori Tanoue, Masaki Yugami, Shihab U Sobuz, Eiichi Hinoi, Yoshifumi Sato, Yuichi Oike, Hiroshi Mizuta, Kazuya Yamagata
Sirtuins (SIRT1-7) are NAD+-dependent deacetylase/deacylases that regulate a wide variety of biological functions. Although the roles of sirtuins in cartilage homeostasis and cartilage diseases have been well studied, there is no information on the contribution of SIRT7 to cartilage homeostasis and osteoarthritis (OA) pathologies. Here, we demonstrate that Sirt7 knockout mice are resistant to the development of aging-associated OA and forced exercise-induced OA. Attenuation of Sirt7 in the murine chondrogenic cell line ATDC5 increased the deposition of a glycosaminoglycan-rich extracellular matrix and the mRNA expression of extracellular matrix components such as Col2a1 and Acan...
February 2, 2018: Biochemical and Biophysical Research Communications
Kazuya Yamagata, Tatsuya Yoshizawa
Sirtuins are a family of evolutionally conserved nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases/deacylases that regulate metabolism. The mammalian sirtuin family consists of seven sirtuins (SIRT1-7). Recent findings have identified critical roles for SIRT1 and SIRT7 in glucose/lipid metabolism in multiple tissues. This review focuses on the metabolic roles of these two sirtuins and the benefits of modulating the activity of sirtuins for the treatment of metabolic diseases such as type 2 diabetes...
2018: International Review of Cell and Molecular Biology
Timothy A Donlon, Brian J Morris, Randi Chen, Kamal H Masaki, Richard C Allsopp, D Craig Willcox, Maarit Tiirikainen, Bradley J Willcox
Longevity is a polygenic trait in which genetic predisposition is particularly important. We hypothesized that amongst genes differentially expressed in response to caloric restriction, several may be candidate longevity genes. We tested 459 single nucleotide polymorphisms (SNPs) in 46 genes differentially expressed in calorically-restricted mice and 12 other genes for association with longevity. Subjects were American men of Japanese ancestry, 440 aged ≥95 years and 374 with an average lifespan. Based on a dominant model of inheritance, an association with longevity at the p < 0...
December 30, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Kun-Lin Chen, Lian Li, Fang-Xiao Yang, Cheng-Min Li, Yi-Ru Wang, Gen-Lin Wang
SIRT7 is a member of the sirtuin family of proteins that are known to be associated with tumor development. However, the functional roles and molecular mechanisms underlying the function of SIRT7 in breast cancer cell survival and tumor development remain unclear. Recent studies demonstrated that SIRT7 is upregulated in breast cancer cells and tissues. In the present study, we systematically explored the roles of SIRT7 in the growth of breast cancer cells and tumors both in vitro and in vivo. Our results showed that SIRT7 plays a major role in facilitating cell survival by promoting cell proliferation and inhibiting apoptosis...
December 12, 2017: Journal of Cellular Physiology
Xin Liu, Liu Yang, Jianfeng Tu, Wenwei Cai, Meiqi Zhang, Zhangxuan Shou, Yingmin Yao, Qiuran Xu
Recent studies have reported that microRNA-526b (miR-526b) is implicated in the growth and metastasis of cancer cells. However, the clinical significance of miR-526b and its role as well as underlying mechanisms are largely unknown in hepatocellular carcinoma (HCC). Here, we detected miR-526b expression difference between HCC and matched nontumor tissues with qRT-PCR. We found that miR-526b displayed lower expression in HCC patient tissues and cells. Clinical analysis revealed that low miR-526b expression correlated with large tumor size, venous infiltration, advanced tumor-node-metastasis (TNM) stage...
October 20, 2017: Oncotarget
Keila Lopes Mendes, Deborah de Farias Lelis, Sérgio Henrique Sousa Santos
The regulation of chronic inflammation has received considerable research attention in recent years because of its contribution to the pathogenesis of chronic diseases such as arthritis, diabetes, metabolic syndrome and obesity. Thus, strategies that inhibit the inflammatory state may be beneficial in improving the pathophysiology of several inflammation-related disorders. Sirtuins are a family of histone deacetylases that contain seven enzymatic activities in mammals (SIRT1-SIRT7) and function to suppress gene transcription by epigenetic mechanisms...
December 2017: Cytokine & Growth Factor Reviews
Kun-Lin Chen, Lian Li, Yi-Ru Wang, Cheng-Min Li, Tarig Mohammed Badri, Gen-Lin Wang
Breast cancer is one of the most common malignant cancers among women and a major clinical obstacle. Although studies have reported the abnormal expression of SIRT7 in breast cancer, whether the function of SIRT7 regulates the expression of long noncoding RNAs (lncRNAs) in breast cancer remains unknown. We aimed to determine the differential expressions of mRNAs and lncRNAs associated with SIRT7 and understand the regulatory mechanism of SIRT7 in breast cancer. RNA sequencing was performed to explore the transcriptome in MDA-MB-231 cells after SIRT7 depletion, and a total of 50,634 different transcripts were identified...
2017: OncoTargets and Therapy
Md Safiqul Islam, Fan-Yan Wei, Kunimasa Ohta, Naoki Shigematsu, Takaichi Fukuda, Kazuhito Tomizawa, Tatsuya Yoshizawa, Kazuya Yamagata
Sirtuin 7 (SIRT7) is an NAD(+)-dependent deacetylase/deacylase, and is involved in a variety of biological processes relevant to the transcription of rRNA, the DNA damage response, tumorigenesis, and metabolism. SIRT7 mRNA is expressed ubiquitously, including in the brain, but there is no detailed information about the anatomical distribution and functional role of SIRT7 in the brain. Here, we demonstrated that SIRT7 is widely expressed in the mouse brain, including in the cortex, striatum, thalamus, hippocampus, and amygdala...
October 31, 2017: Biochemical and Biophysical Research Communications
Romain Haider, Fabienne Massa, Lisa Kaminski, Stephan Clavel, Zied Djabari, Guillaume Robert, Kathiane Laurent, Jean-François Michiels, Matthieu Durand, Jean-Ehrland Ricci, Jean-François Tanti, Frédéric Bost, Damien Ambrosetti
Predictive biomarkers for advanced prostate cancer (PCa) are still missing. The sirtuin 7 (SIRT7) has been linked to tumorogenesis but its role in prostate cancer is poorly documented. To determine if SIRT7 can be a biomarker for aggressive prostate cancer and plays a role in PCa aggressiveness. We analyzed the expression of SIRT7 by immunohistochemistry in 57 patients comparing healthy with adjacent cancer tissue. SIRT7 levels were significantly elevated in tumors and its expression was positively associated with the grade...
September 29, 2017: Oncotarget
Wang Wei, Zhang Xiao Jing, Zheng Ke, Pei Yi
It is still a controversy whether the role of Sirtuin 7 (SIRT7) is an oncogene or a tumor suppressor gene in cancer as SIRT7 may have different functions in different types of cancer. Particularly, the specific roles of SIRT7 in the progression of osteosarcoma remain undiscovered. The main aim of this study is to identify the expression of SIRT7 in osteosarcoma and explore the biological functions of SIRT7 in regulating cellular processes of osteosarcoma cells. Here, we show that SIRT7 expression was significantly higher in osteosarcoma tissues and osteosarcoma cell lines than in non-tumor tissues and an immortalized normal cell line, respectively...
2017: American Journal of Cancer Research
Di Li, Lifei Li
The abnormal expression of microRNAs (miRNAs) is associated with cancer initiation and progression. miRNAs functioning as oncogenes or tumor suppressors represent novel biomarkers for cancer diagnosis, prognosis, and serve as therapeutic tools. MiR‑3666 has been reported as a tumor suppressor in various types of cancer; however, its role in breast cancer remains unknown. In the current study, the aim was to investigate the potential role of miR‑3666 in breast cancer. It was identified that miR‑3666 was decreased in breast cancer cell lines and that the overexpression of miR‑3666 inhibited breast cancer cell proliferation...
December 2017: Molecular Medicine Reports
Nicolas Burg, Stefan Bittner, Erik Ellwardt
Epigenetic regulators are increasingly recognized as relevant modulators in the immune and nervous system. The class of sirtuins consists of NAD+-dependent histone deacetylases that regulate transcription. Sirtuin family member Sirt1 has already been shown to influence the disease course in an animal model of autoimmune neuroinflammation (experimental autoimmune encephalomyelitis (EAE). A role of Sirt7, a related epigenetic regulator, on immune system regulation has been proposed before, as these mice are more susceptible to develop inflammatory cardiomyopathy...
September 20, 2017: Neuroscience Research
Jian Fang, Alessandro Ianni, Christian Smolka, Olesya Vakhrusheva, Hendrik Nolte, Marcus Krüger, Astrid Wietelmann, Nicolas G Simonet, Juan M Adrian-Segarra, Alejandro Vaquero, Thomas Braun, Eva Bober
Sirtuins (Sirt1-Sirt7) are NAD(+)-dependent protein deacetylases/ADP ribosyltransferases, which play decisive roles in chromatin silencing, cell cycle regulation, cellular differentiation, and metabolism. Different sirtuins control similar cellular processes, suggesting a coordinated mode of action but information about potential cross-regulatory interactions within the sirtuin family is still limited. Here, we demonstrate that Sirt1 requires autodeacetylation to efficiently deacetylate targets such as p53, H3K9, and H4K16...
October 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
Xiao Chen, Wen-Feng Li, Xiaoli Wu, Heng-Chao Zhang, Li Chen, Pei-Ying Zhang, Li-Yuan Liu, Di Ma, Tongke Chen, Lingli Zhou, Yunsheng Xu, Meng-Tao Zhou, Kai-Fu Tang
DNA double-strand break (DSB) repair is an important mechanism underlying chemotherapy resistance in human cancers. Dicer participates in DSB repair by facilitating homologous recombination. However, whether Dicer is involved in non-homologous end joining (NHEJ) remains unknown. Here, we addressed whether Dicer regulates NHEJ and chemosensitivity in colon cancer cells. Using our recently developed NHEJ assay, we found that DSB introduction by I-SceI cleavage leads to Dicer upregulation. Dicer knockdown increased SIRT7 binding and decreased the level of H3K18Ac (acetylated lysine 18 of histone H3) at DSB sites, thereby repressing the recruitment of NHEJ factors to DSB sites and inhibiting NHEJ...
September 1, 2017: Carcinogenesis
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