SIRT2 mediated downregulation of FOXM1 in response to TGFβ through the RAF-MEK-ERK signaling pathway in colon cancer

IF 0.7 4区生物学 Q4 BIOLOGY

Archives of Biological Sciences Pub Date : 2021-01-01 DOI:10.2298/ABS210227020O

Ozkan Ozden, S. Park

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引用次数: 3

Abstract

The transcription factor forkhead box M1 (FOXM1) is frequently upregulated in many solid tumors, including those in the colon. As a master regulator, the sirtuin (SIRT) protein family is comprised of seven nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases/adenosine diphosphate (ADP) ribosyl transferases whose activities are associated with aging and cancer. In this study, we determined whether a cytoplasmic member of SIRTs, SIRT2, influences the expression of oncogenic FOXM1 in colon cancer in vitro. The association of SIRT2 and FOXM1 were analyzed using SIRT2 knockout mouse embryonic fibroblasts and SIRT2 knocked-down and overexpressing HCT116 colon cancer cell lines. Cell lines were treated with 10 ng/mL transforming growth factor-beta (TGFR) for 24 h. SIRT2 could downregulate FOXM1 through the TGF? mitogen-activated protein kinase (RAF-MEK-ERK) signaling pathway in genetically altered mouse embryonic fibroblasts and colon cancer cell lines. The indirect association between SIRT2 and FOXM1 through TGF? may be important because activators or inhibitors of SIRT2 could provide a potential approach to downregulate FOXM1 in gastrointestinal cancers.

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在结肠癌中，SIRT2通过RAF-MEK-ERK信号通路介导FOXM1对TGFβ的下调

转录因子叉头盒M1 (FOXM1)在包括结肠在内的许多实体肿瘤中经常上调。sirtuin (SIRT)蛋白家族由7个烟酰胺腺嘌呤二核苷酸(NAD+)依赖的去乙酰化酶/二磷酸腺苷(ADP)核糖基转移酶组成，其活性与衰老和癌症有关。在这项研究中，我们确定了SIRTs的细胞质成员SIRT2是否影响结肠癌中致癌FOXM1的表达。使用SIRT2敲除小鼠胚胎成纤维细胞和SIRT2敲除和过表达HCT116结肠癌细胞系分析SIRT2和FOXM1的关联。10 ng/mL转化生长因子- β (TGFR)处理细胞系24小时，SIRT2可通过TGF?基因改变小鼠胚胎成纤维细胞和结肠癌细胞系中的丝裂原活化蛋白激酶(RAF-MEK-ERK)信号通路SIRT2与FOXM1通过TGF?可能很重要，因为SIRT2的激活剂或抑制剂可能为下调胃肠道癌症中的FOXM1提供了一种潜在的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Archives of Biological Sciences 生物-生物学

CiteScore

1.40

自引率

0.00%

发文量

审稿时长

3-8 weeks

期刊介绍： The Archives of Biological Sciences is a multidisciplinary journal that covers original research in a wide range of subjects in life science, including biology, ecology, human biology and biomedical research. The Archives of Biological Sciences features articles in genetics, botany and zoology (including higher and lower terrestrial and aquatic plants and animals, prokaryote biology, algology, mycology, entomology, etc.); biological systematics; evolution; biochemistry, molecular and cell biology, including all aspects of normal cell functioning, from embryonic to differentiated tissues and in different pathological states; physiology, including chronobiology, thermal biology, cryobiology; radiobiology; neurobiology; immunology, including human immunology; human biology, including the biological basis of specific human pathologies and disease management.