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紫外辐射下人角质形成细胞中类菌孢素氨基酸(MAA)紫菜素-334的综合表达谱分析及功能网络分析

Comprehensive Expression Profiling and Functional Network Analysis of Porphyra-334, One Mycosporine-Like Amino Acid (MAA), in Human Keratinocyte Exposed with UV-radiation.

作者信息

Suh Sung-Suk, Lee Sung Gu, Youn Ui Joung, Han Se Jong, Kim Il-Chan, Kim Sanghee

机构信息

Division of Polar Life Sciences, Korea Polar Research Institute, Incheon 21990, Korea.

Department of Polar Science, University of Science and Technology, Incheon 21990, Korea.

出版信息

Mar Drugs. 2017 Jun 24;15(7):196. doi: 10.3390/md15070196.

Abstract

Mycosporine-like amino acids (MAAs) have been highlighted as pharmacologically active secondary compounds to protect cells from harmful UV-radiation by absorbing its energy. Previous studies have mostly focused on characterizing their physiological properties such as antioxidant activity and osmotic regulation. However, molecular mechanisms underlying their UV-protective capability have not yet been revealed. In the present study, we investigated the expression profiling of porphyra-334-modulated genes or microRNA (miRNAs) in response to UV-exposure and their functional networks, using cDNA and miRNAs microarray. Based on our data, we showed that porphyra-334-regulated genes play essential roles in UV-affected biological processes such as Wnt (Wingless/integrase-1) and Notch pathways which exhibit antagonistic relationship in various biological processes; the UV-repressed genes were in the Wnt signaling pathway, while the activated genes were in the Notch signaling. In addition, porphyra-334-regulated miRNAs can target many genes related with UV-mediated biological processes such as apoptosis, cell proliferation and translational elongation. Notably, we observed that functional roles of the target genes for up-regulated miRNAs are inversely correlated with those for down-regulated miRNAs; the former genes promote apoptosis and translational elongation, whereas the latter function as inhibitors in these processes. Taken together, these data suggest that porphyra-334 protects cells from harmful UV radiation through the comprehensive modulation of expression patterns of genes involved in UV-mediated biological processes, and that provide a new insight to understand its functional molecular networks.

摘要

类菌孢素氨基酸(MAAs)已被视为具有药理活性的次生化合物,可通过吸收能量来保护细胞免受有害紫外线辐射。以往的研究大多集中于表征其生理特性,如抗氧化活性和渗透调节。然而,其紫外线防护能力的分子机制尚未揭示。在本研究中,我们利用cDNA和miRNA微阵列,研究了紫菜-334调节的基因或微小RNA(miRNA)在紫外线照射下的表达谱及其功能网络。基于我们的数据,我们发现紫菜-334调节的基因在受紫外线影响的生物过程中发挥重要作用,如Wnt(无翅/整合酶-1)和Notch信号通路,它们在各种生物过程中表现出拮抗关系;紫外线抑制的基因在Wnt信号通路中,而激活的基因在Notch信号通路中。此外,紫菜-334调节的miRNA可以靶向许多与紫外线介导的生物过程相关的基因,如细胞凋亡、细胞增殖和翻译延伸。值得注意的是,我们观察到上调miRNA的靶基因的功能作用与下调miRNA的靶基因的功能作用呈负相关;前者促进细胞凋亡和翻译延伸,而后者在这些过程中起抑制作用。综上所述,这些数据表明紫菜-334通过全面调节参与紫外线介导的生物过程的基因表达模式来保护细胞免受有害紫外线辐射,并为理解其功能分子网络提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/012c/5532638/96143df19e47/marinedrugs-15-00196-g001.jpg

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