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RETRACTED ARTICLE: Aberrant Methylation of miR-34b and IL-12B mRNA Promoters Contributes to the Reduced Severity of Ankylosing Spondylitis

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Abstract

DNA methylation of Interleukin-12B (IL-12B) and miR-34b was proved to affect the expression of IL-12B and miR-34b, which were found to be involved in the pathogenesis of ankylosing spondylitis (AS). However, the molecular mechanisms underlying the role of IL-12B and miR-34b in AS remain to be explored. AS patients were divided into four groups according to their status of DNA methylation of miR-34b and IL-12B by bisulfite sequencing: HYPER-miR-34b + HYPO-IL-12B, HYPER-miR-34b + HYPER-IL-12B, HYPO-miR-34b + HYPER-IL-12B and HYPO-miR-34b + HYPO-IL-12B groups. Functional indicators were examined for patients with different status of DNA methylation in their miR-34b and IL-12B promoters. QPCR was performed to examine the expression of miR-34b and IL-12B mRNA under different conditions. ELISA was used to measure the expression of IL-12B p40 in the peripheral blood. Western blot was used to analyze the expression of IL-12B proteins. Luciferase assay was carried out to explore the suppressive role of miR-34b in IL-12B expression. The level of Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) was gradually increased in HYPER-miR-34b + HYPO-IL-12B,HYPER-miR-34b + HYPER-IL-12B,HYPO-miR-34b + HYPER-IL-12B and HYPO-miR-34b + HYPO-IL-12B groups, whereas the levels of Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) were significantly elevated in the HYPO-miR-34b + HYPO-IL-12B group and diminished in the HYPER-miR-34b + HYPO-IL-12B group. The expression of miR-34b in the PBMCs and peripheral blood was remarkably higher in the HYPER-miR-34b + HYPO-IL-12B and HYPER-miR-34b + HYPER-IL-12B groups, whereas the expression of IL-12B was gradually decreased in the HYPER-miR-34b + HYPO-IL-12B, HYPER-miR-34b + HYPER-IL-12B, HYPO-miR-34b + HYPER-IL-12B and HYPO-miR-34b + HYPO-IL-12B groups. Luciferase assays with the transfection of miR-34b precursors suggested that miR-34b strongly suppressed the expression of IL-12B in THP-1 cells. In conclusion, our study demonstrated that hypermethylated miR-34b promoter led to evident upregulation of miR-34b, thus inhibiting the expression of IL-12B and alleviated the severity of ankylosing spondylitis by reducing the levels of factors including ASDAS-CRP, BASFI and BASMI.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Change history

Abbreviations

AS:

Ankylosing spondylitis

IL-12B:

Interleukin-12B

PBMC:

Peripheral blood monocyte

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Authors and Affiliations

  1. Department of Rheumatology, Qilu Hospital, Shandong University, No. 107 Wenhua West Road, Lixia District, Jinan City, Shandong Province, China

    Shan Meng & Qiang Shu

  2. Institute of Orthopedics, Chinese People’s Liberation Army, Beijing, China

    Shaoguang Fan

  3. Department of Rheumatology, Yantai-Mountain Hospital, Yantai, China

    Yanmei Li

  4. Department of Rheumatology, Affiliated Hospital of Weifang Medical College, Weifang, China

    Donghua Xu, Xiufen Ma, Yuhua Su, Yajing Liu & Chunxiao Guan

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  1. Shan Meng
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  2. Shaoguang Fan
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  3. Yanmei Li
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  4. Donghua Xu
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  9. Qiang Shu
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Contributions

QS and SM planned the study, SGF and YML collected the literatures, DHX and XFM collected and analyzed the data, YHS CHX and YJL composed the manuscript, and all the other co-authors approved the final manuscript.

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Correspondence to Qiang Shu.

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This article has been retracted. Please see the retraction notice for more detail:https://doi.org/10.1007/s10528-022-10305-5

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Meng, S., Fan, S., Li, Y. et al. RETRACTED ARTICLE: Aberrant Methylation of miR-34b and IL-12B mRNA Promoters Contributes to the Reduced Severity of Ankylosing Spondylitis. Biochem Genet 59, 714–730 (2021). https://doi.org/10.1007/s10528-020-10023-w

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