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未分化和分化的 House Ear Institute-Organ of Corti 1(HEI-OC1)细胞的 microRNA 特征和细胞特性。

MicroRNA Signature and Cellular Characterization of Undifferentiated and Differentiated House Ear Institute-Organ of Corti 1 (HEI-OC1) Cells.

机构信息

Division of Otolaryngology - Head & Neck Surgery, Department of Surgery, Faculty of Medicine, The University of British Columbia, Vancouver, BC, V5Z IM9, Canada.

Division of Otolaryngology - Head & Neck Surgery, Diamond Health Care Centre, Vancouver General Hospital, 4th Floor-2775 Laurel Street, BC, V5Z IM9, Vancouver, Canada.

出版信息

J Assoc Res Otolaryngol. 2022 Aug;23(4):467-489. doi: 10.1007/s10162-022-00850-6. Epub 2022 May 11.

DOI:10.1007/s10162-022-00850-6
PMID:35546217
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9094604/
Abstract

MicroRNAs (miRNAs) regulate gene expressions and control a wide variety of cellular functions. House Ear Institute-Organ of Corti 1 (HEI-OC1) cells are widely used to screen ototoxic drugs and to investigate cellular and genetic alterations in response to various conditions. HEI-OC1 cells are almost exclusively studied under permissive conditions that promote cell replication at the expense of differentiation. Many researchers suggest that permissive culture condition findings are relevant to understanding human hearing disorders. The mature human cochlea however consists of differentiated cells and lacks proliferative capacity. This study therefore aimed to compare the miRNA profiles and cellular characteristics of HEI-OC1 cells cultured under permissive (P-HEI-OC1) and non-permissive (NP-HEI-OC1) conditions. A significant increase in the level of expression of tubulin β1 class VI (Tubb1), e-cadherin (Cdh1), espin (Espn), and SRY (sex determining region Y)-box2 (Sox2) mRNAs was identified in non-permissive cells compared with permissive cells (P < 0.05, Kruskal-Wallis H test, 2-sided). miR-200 family, miR-34b/c, and miR-449a/b functionally related cluster miRNAs, rodent-specific maternally imprinted gene Sfmbt2 intron 10 cluster miRNAs (-466a/ -467a), and miR-17 family were significantly (P < 0.05, Welch's t-test, 2-tailed) differentially expressed in non-permissive cells when compared with permissive cells. Putative target genes were significantly predominantly enriched in mitogen-activated protein kinase (MAPK), epidermal growth factor family of receptor tyrosine kinases (ErbB), and Ras signaling pathways in non-permissive cells compared with permissive cells. This distinct miRNA signature of differentiated HEI-OC1 cells could help in understanding miRNA-mediated cellular responses in the adult cochlea.

摘要

微小 RNA(miRNA)调节基因表达,控制着多种细胞功能。House Ear Institute-Organ of Corti 1(HEI-OC1)细胞广泛用于筛选耳毒性药物,并研究各种条件下细胞和遗传变化。HEI-OC1 细胞几乎仅在促进细胞复制而牺牲分化的允许条件下进行研究。许多研究人员认为,允许培养条件下的发现与理解人类听力障碍有关。然而,成熟的人耳蜗由分化细胞组成,缺乏增殖能力。因此,本研究旨在比较在允许条件(P-HEI-OC1)和非允许条件(NP-HEI-OC1)下培养的 HEI-OC1 细胞的 miRNA 谱和细胞特征。与允许细胞相比,非允许细胞中转录本 Tubulin β1 类 VI(Tubb1)、E-钙黏蛋白(Cdh1)、Espin(Espn)和性别决定区 Y 框 2(Sox2)mRNA 的表达水平显著增加(P<0.05,Kruskal-Wallis H 检验,双侧)。与允许细胞相比,非允许细胞中 miR-200 家族、miR-34b/c 和 miR-449a/b 功能相关簇 miRNA、啮齿动物特异性母性印迹基因 Sfmbt2 内含子 10 簇 miRNA(-466a/-467a)和 miR-17 家族显著差异表达(P<0.05,Welch's t 检验,双侧)。与允许细胞相比,非允许细胞中假定的靶基因显著主要富集于丝裂原激活蛋白激酶(MAPK)、表皮生长因子受体酪氨酸激酶家族(ErbB)和 Ras 信号通路。非允许细胞中分化的 HEI-OC1 细胞的这种独特 miRNA 特征有助于理解成年耳蜗中 miRNA 介导的细胞反应。

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