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lncRNA MIR155HG Alleviates Depression-Like Behaviors in Mice by Regulating the miR-155/BDNF Axis

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Abstract

Depression is one of most common psychiatric disorders, and the detailed molecular mechanism remains to be fully elucidated. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophic factor that is decreased and closely involved in the development of depression. Noncoding RNAs are central regulators of cellular activities that modulate target genes. However, the roles of long noncoding RNA (lncRNA) MIR155HG and miRNA-155 (miR-155) in the pathophysiology of depression are unclear. In the present study, we aimed to explore the effects of lncRNA MIR155HG and miR-155 on the development of depression and uncover the underlying molecular mechanism. Real-time quantitative polymerase chain reaction was used to examine the expression of MIR155HG and miR-155. Western blotting was applied to measure the expression of BDNF. A luciferase reporter assay was utilized to determine the regulatory relationship between MIR155HG and miR-155. Our current work found that lncRNA MIR155HG and BDNF levels decreased while miR-155 levels increased in the hippocampal region of CUMS (chronic unpredictable mild stress) mice, a well-accepted mouse model of depression. Moreover, MIR155HG rescued while miR-155 exacerbated the depression-like behaviors of CUMS mice. Through bioinformatics analysis and luciferase reporter assays, we found that MIR155HG directly bound to and negatively modulated the expression of miR-155. Moreover, increased miR-155 was found to repress the expression of BDNF, a critical neurotrophic factor that has been reported to alleviate the depression-like behaviors of CUMS mice. Our present study revealed that lncRNA MIR155HG protected CUMS mice by regulating the miR-155/BDNF axis. Our study aimed to understand the pathophysiology of depression and provided potential therapeutic targets to diagnose and treat depression.

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Data Availability

All data and materials in this study are available upon request.

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Funding

Key development projects in Shaanxi Province, S2018-YF-YBSF-0830.

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Authors and Affiliations

  1. Department of Psychology and Psychiatry, The Second Affiliated Hospital of Xi’an Jiaotong University College of Medicine, Xian, 710004, China

    Zhang Huan, Zhu Mei, Ma Xinxin, Wang Yaping, Liu Ling & Wang Lei

  2. Core Research Laboratory, The Second Affiliated Hospital, College of Medicine, Jiaotong University, Xi’an, 710004, Shaanxi, China

    Huang Na

  3. School of Medicine, Northwest University, Xi’an, 710069, China

    Zhang Kejin

  4. Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University College of Medicine, Xian, 710069, China

    Liu Yanan

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  1. Zhang Huan
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  2. Zhu Mei
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Contributions

L.Y. and Z.K.: conceptualization, methodology, and writing (reviewing and editing). Z.H., L.Y.: investigation, data curation, and writing (original draft preparation). Z.M., H.N.: visualization and investigation. M.X., W.Y.: visualization and supervision. L.L., W.L.: software and validation.

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Correspondence to Liu Yanan.

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The authors declare no conflicts of interest.

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The animal experiments performed in this study were approved by the Institute for Experimental Animals of Xi’an Jiaotong University.

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Huan, Z., Mei, Z., Na, H. et al. lncRNA MIR155HG Alleviates Depression-Like Behaviors in Mice by Regulating the miR-155/BDNF Axis. Neurochem Res 46, 935–944 (2021). https://doi.org/10.1007/s11064-021-03234-z

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