Hu Yiwang, Lin Jiahao, Lin Yao, Chen Xuxu, Zhu Guanbao, Huang Guoyu
Department of Colorectal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
School of The First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Oncol Lett. 2019 Feb;17(2):2171-2176. doi: 10.3892/ol.2018.9877. Epub 2018 Dec 28.
The sirtuins (SIRTs) are a family of nicotinamide-adenine dinucleotide (NAD)-dependent protein deacetylases. SIRT4 is a mitochondrial NAD-dependent adenosine diphsophate-ribosyltransferase. Recent studies demonstrated that SIRT4 can regulate glutamine metabolism and thus act as a tumor suppressor. However, the association of SIRT4 with gastric cancer remains unknown. The present study investigated the potential role of SIRT4 in the proliferation of human gastric cancer cells. Gastric cancer cell lines (SGC-7901 and MNK45) overexpressing SIRT4 were established by lentiviral infection. The effect of overexpression of SIRT4 in gastric cancer was evaluated by determining the cell viability, proliferation activity and colony-forming ability of gastric cancer cells . Furthermore, the cell cycle profiles of SGC-7901 and MNK45 cells overexpressing SIRT4 were evaluated to provide insights into potential underlying molecular mechanisms. Overexpression of SIRT4 significantly inhibited the proliferation and colony-forming ability of the gastric cancer cells . Furthermore, overexpression of SIRT4 induced G1 cell cycle arrest via suppression of phosphorylated extracellular signal-regulated kinase, cyclin D and cyclin E. In conclusion, the results of the present study indicated that SIRT4 may function as a tumor suppressor in gastric cancer by regulating cell proliferation, therefore SIRT4 may be a potential therapeutic target against this disease.
沉默调节蛋白（SIRTs）是一类烟酰胺腺嘌呤二核苷酸（NAD）依赖性蛋白脱乙酰酶。SIRT4是一种线粒体NAD依赖性二磷酸腺苷核糖基转移酶。最近的研究表明，SIRT4可以调节谷氨酰胺代谢，从而起到肿瘤抑制作用。然而，SIRT4与胃癌的关系尚不清楚。本研究调查了SIRT4在人胃癌细胞增殖中的潜在作用。通过慢病毒感染建立了过表达SIRT4的胃癌细胞系（SGC - 7901和MNK45）。通过测定胃癌细胞的细胞活力、增殖活性和集落形成能力来评估SIRT4过表达在胃癌中的作用。此外，评估了过表达SIRT4的SGC - 7901和MNK45细胞的细胞周期分布，以深入了解潜在的分子机制。SIRT4的过表达显著抑制了胃癌细胞的增殖和集落形成能力。此外，SIRT4的过表达通过抑制磷酸化的细胞外信号调节激酶、细胞周期蛋白D和细胞周期蛋白E诱导G1期细胞周期阻滞。总之，本研究结果表明，SIRT4可能通过调节细胞增殖在胃癌中发挥肿瘤抑制作用，因此SIRT4可能是针对这种疾病的潜在治疗靶点。
