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半滑舌鳎24-脱氢胆固醇还原酶的特性:表达谱、表观遗传修饰及其敲低效应

Characterization of Chinese tongue sole (Cynoglossus semilaevis) 24-dehydrocholesterol reductase: Expression profile, epigenetic modification, and its knock-down effect.

作者信息

Wang Na, Gong Zhihong, Wang Jialin, Xu Wenteng, Yang Qian, Chen Songlin

机构信息

Key Laboratory for Sustainable Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266235, China; Shandong Key Laboratory of Marine Fisheries Biotechnology and Genetic Breeding, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China.

Key Laboratory for Sustainable Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China.

出版信息

Gen Comp Endocrinol. 2021 Oct 1;312:113870. doi: 10.1016/j.ygcen.2021.113870. Epub 2021 Jul 26.

DOI:10.1016/j.ygcen.2021.113870
PMID:34324841
Abstract

The sexual size dimorphism of the Chinese tongue sole (Cynoglossus semilaevis) has greatly obstructed its sustainable development; however, the underlying mechanism remains unclear. Based on C. semilaevis transcriptomic information, 24-dehydrocholesterol reductase (dhcr24) was identified in steroid biosynthesis, showing female-liver-biased expression. Dhcr24 has been reported to participate in various processes, such as cholesterol synthesis, oxidative stress response, neuroprotection, and cell survival. The present study assessed its role in the sexual size dimorphism in fish. First, detailed expression pattern analysis showed that dhcr24 mRNAs were extensively expressed in tissues and the highest levels were found in the liver and gonads of females. Analysis of the dhcr24 promoter region demonstrated different DNA methylation statuses in female, male, and pseudomale gonads with higher epigenetic modification in males. The confirmation of transcription activity of the dhcr24 promoter and putative transcription factors (e.g., ER, AR, SREBP, and POU1F1a) provides the foundation for studying its regulatory mechanism. Finally, dhcr24-siRNA mediated knock-down assay using C. semilaevis liver cells showed that steroid biosynthesis related genes (e.g., ebp, dhcr7, and sc5d), core component of PI3K/Akt pathway (e.g., pi3k), and igf1r exhibited different expression patterns. Further investigation on the interplay between steroid hormones, dhcr24, PI3K/Akt, and IGF-1 systems will be valuable to better understand the mechanism underlying the sexual size dimorphism in C. semilaevis.

摘要

半滑舌鳎(Cynoglossus semilaevis)的两性体型差异极大地阻碍了其可持续发展;然而,其潜在机制仍不清楚。基于半滑舌鳎的转录组信息,在类固醇生物合成过程中鉴定出了24-脱氢胆固醇还原酶(dhcr24),该酶在雌性肝脏中表达偏向性较高。据报道,Dhcr24参与多种过程,如胆固醇合成、氧化应激反应、神经保护和细胞存活。本研究评估了其在鱼类两性体型差异中的作用。首先,详细的表达模式分析表明,dhcr24 mRNA在组织中广泛表达,在雌性的肝脏和性腺中表达水平最高。对dhcr24启动子区域的分析表明,雌性、雄性和伪雄性性腺中的DNA甲基化状态不同,雄性的表观遗传修饰程度更高。对dhcr24启动子和推定转录因子(如ER、AR、SREBP和POU1F1a)转录活性的确认,为研究其调控机制奠定了基础。最后,使用半滑舌鳎肝细胞进行的dhcr24-siRNA介导的敲低试验表明,类固醇生物合成相关基因(如ebp、dhcr7和sc5d)、PI3K/Akt途径的核心成分(如pi3k)和igf1r呈现出不同的表达模式。进一步研究类固醇激素、dhcr24、PI3K/Akt和IGF-1系统之间的相互作用,对于更好地理解半滑舌鳎两性体型差异的潜在机制具有重要意义。

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