miR221 regulates cell migration by targeting annexin a1 expression in human mesothelial MeT-5A cells neoplastic-like transformed by multi-walled carbon nanotube.

IF 2.7 4区 医学 Q2 GENETICS & HEREDITY
Li Ju, Lijin Zhu, Hao Wu, Min Yu, Xianhong Yin, Zhenyu Jia, Lingfang Feng, Shibo Ying, Hailing Xia, Shuzhi Zhang, Jianlin Lou, Jun Yang
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引用次数: 2

Abstract

Background: Multi-walled carbon nanotube (MWCNT) is one of the most widely used manufactured nanomaterials, however, its potential harmful effect on human health is of great concern. Previously we have shown the acute and chronic exposure to MWCNT induced different responses in human mesothelial MeT-5A cells. In the current study, MeT-5A cells were continuously subjected to MWCNT exposure at 10 μg/cm2 for 48 h per passage, up to a whole year, to further clarify the carcinogesis and its potential mechanisms of MWCNT.

Results: After one-year MWCNT treatment, MeT-5A cells exhibited neoplastic-like properties, including morphological changes, anchorage-independent growth, increased cell proliferation and cell migration. Further examination revealed the expression of microRNA 221 (miR221) was gradually decreased, while the annexin a1 expression was increased at both the mRNA and protein level during the exposure. Bioinformatic analysis indicated that annexin a1 is a target for miR221 regulation, and it was confirmed by transfecting cells with miR221 mimics, which resulted in the downregulation of annexin a1. Detailed analyses demonstrated miR221 was involved in the regulation of cell migration, e.g., downregulation of miR221 or overexpression of ANNEXIN A1, contributed to the increased cell migration. In contrast, overexpression of miR221 or downregulation of ANNEXIN A1 slowed cell migration.

Conclusions: Taken together, these results point to a neoplastic-transforming property of MWCNT, and the miR221-annexin a1 axis is involved in the regulation of cell migration in the transformed cells.

miR221通过靶向多壁碳纳米管转化的人间皮MeT-5A细胞中膜联蛋白a1的表达调控细胞迁移。
背景:多壁碳纳米管(MWCNT)是应用最广泛的人造纳米材料之一,但其对人体健康的潜在危害一直备受关注。以前,我们已经证明急性和慢性暴露于MWCNT诱导人间皮MeT-5A细胞的不同反应。在本研究中,MeT-5A细胞以10 μg/cm2的浓度连续暴露于MWCNT,每次48小时,长达一年,以进一步阐明MWCNT的致癌作用及其潜在机制。结果:MWCNT处理1年后,MeT-5A细胞表现出肿瘤样特性,包括形态改变、不依赖锚定生长、细胞增殖和细胞迁移增加。进一步检查发现,在暴露期间,microRNA 221 (miR221)的表达逐渐降低,而膜联蛋白a1的mRNA和蛋白水平表达均升高。生物信息学分析表明,膜联蛋白a1是miR221调控的靶点,并通过转染miR221模拟物证实了这一点,导致膜联蛋白a1下调。详细的分析表明,miR221参与了细胞迁移的调节,例如miR221的下调或ANNEXIN A1的过表达导致了细胞迁移的增加。相反,miR221过表达或ANNEXIN A1下调会减缓细胞迁移。综上所述,这些结果表明MWCNT具有肿瘤转化特性,mir221 -膜联蛋白a1轴参与了转化细胞中细胞迁移的调控。
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
Genes and Environment
Genes and Environment Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.00
自引率
0.00%
发文量
24
审稿时长
27 weeks
期刊介绍: Genes and Environment is an open access, peer-reviewed journal that aims to accelerate communications among global scientists working in the field of genes and environment. The journal publishes articles across a broad range of topics including environmental mutagenesis and carcinogenesis, environmental genomics and epigenetics, molecular epidemiology, genetic toxicology and regulatory sciences. Topics published in the journal include, but are not limited to, mutagenesis and anti-mutagenesis in bacteria; genotoxicity in mammalian somatic cells; genotoxicity in germ cells; replication and repair; DNA damage; metabolic activation and inactivation; water and air pollution; ROS, NO and photoactivation; pharmaceuticals and anticancer agents; radiation; endocrine disrupters; indirect mutagenesis; threshold; new techniques for environmental mutagenesis studies; DNA methylation (enzymatic); structure activity relationship; chemoprevention of cancer; regulatory science. Genetic toxicology including risk evaluation for human health, validation studies on testing methods and subjects of guidelines for regulation of chemicals are also within its scope.
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