Long Noncoding RNA lnc-TCEA1-3 Affects Osteoclastic Function by Regulating ATP6V1H.

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Critical Reviews in Eukaryotic Gene Expression Pub Date : 2024-01-01 DOI:10.1615/CritRevEukaryotGeneExpr.2023048669
Yuzhuan Hou, Shaoqing Yang, Zanyan Zhao, Yongqing Huang, Yanli Zhang, Wenyan Ruan, Xiaohong Duan
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Abstract

H subunit of V-ATPase (ATP6V1H) is specifically expressed in osteoclasts and its deficiency lead to osteoporosis. Our group previously found four intronic SNPs of ATP6V1H related to reduced bone mineral density, but the mechanisms was not clear. In this study, we found that the above four SNPs were located at lncRNA lnc-TCEA1-3 by using bioinformatics analysis. We further detected the function of lnc-TCEA1-3 on regulating ATP6V1H and osteoclast function using Atp6v1h knockout mice, lentivirus transfection and qPCR analysis. Over expression of lnc-TCEA1-3 up regulated the expression of ATP6V1H in HEK293 cells, HOS cells and primarily cultured osteoclasts, and increased the number of primarily cultured osteoclasts. In addition, over expression of lnc-TCEA1-3 exerted distinct effect on two transcripts of ATP6V1H in HEK293, HOS and osteoclasts. This study will facilitate the in-depth analysis of the effects of ATP6V1H on bone diseases, and discover new therapeutic strategies.

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长非编码RNA lnc-TCEA1-3通过调节ATP6V1H影响成骨细胞功能。
V-ATP酶H亚基(ATP6V1H)在破骨细胞中特异性表达,其缺乏导致骨质疏松。我们的研究小组先前发现ATP6V1H的四个内含子SNPs与骨密度降低有关,但其机制尚不清楚。在本研究中,我们通过生物信息学分析发现,上述四个SNPs位于lncRNA lnc-TCEA1-3。我们使用ATP6V1H敲除小鼠、慢病毒转染和qPCR分析进一步检测了lnc-TCEA1-3对ATP6V1H和破骨细胞功能的调节作用。lnc-TCEA1-3的过表达上调了HEK293细胞、HOS细胞和原代培养破骨细胞中ATP6V1H的表达,并增加了原代培养的破骨细胞的数量。此外,lnc-TCEA1-3的过表达对HEK293、HOS和破骨细胞中ATP6V1H的两个转录物产生了不同的影响。本研究将有助于深入分析ATP6V1H对骨病的影响,并发现新的治疗策略。
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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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