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Circular RNA circ_0008360 Inhibits the Proliferation, Migration, and Inflammation and Promotes Apoptosis of Fibroblast-Like Synoviocytes by Regulating miR-135b-5p/HDAC4 Axis in Rheumatoid Arthritis

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Abstract—

Circular RNAs (circRNAs) have been demonstrated to play crucial roles in the development and progression of many diseases, including rheumatoid arthritis (RA). However, the functions and molecular mechanism of circ_0008360 in RA remain unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of circ_0008360, microRNA-135b-5p (miR-135b-5p), and histone deacetylase 4 (HDAC4). Cell Counting Kit-8 (CCK-8) assay, wound healing assay, and flow cytometry analysis were performed to assess cell proliferation, migration, and apoptosis, respectively. Inflammatory response was evaluated by enzyme-linked immunosorbent assay (ELISA). The interaction between miR-135b-5p and circ_0008360 or HDAC4 was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) and RNA pull-down assays. Western blot assay was used to detect the protein expression of HDAC4 and proliferating cell nuclear antigen (PCNA). The expression of circ_0008360 was downregulated in RA synovial tissues and RA fibroblast-like synoviocytes (RA-FLSs). Circ_0008360 suppressed the proliferation, migration, and inflammation and promoted apoptosis of RA-FLSs, and circ_0008360 knockdown showed opposite effects. Moreover, miR-135b-5p was a direct target of circ_0008360, and miR-135b-5p could reverse the effects of circ_0008360 on proliferation, migration, inflammation, and apoptosis in RA-FLSs. Furthermore, HDAC4 was a downstream target of miR-135b-5p, and miR-135b-5p accelerated the proliferation, migration, and inflammation and suppressed apoptosis of RA-FLSs by targeting HDAC4. In addition, circ_0008360 positively regulated HDAC4 expression by sponging miR-135b-5p. Circ_0008360 inhibited the proliferation, migration, and inflammation and facilitated apoptosis of RA-FLSs by sponging miR-135b-5p and upregulating HDAC4, providing a potential target for prevention and treatment of RA.

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Availability of Data and Materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author information

Author notes

  1. Jinying Hao and Yan Chen are contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology, Heping Hospital Affiliated To Changzhi Medical College, Changzhi, Shanxi, China

    Jinying Hao

  2. Department of Rheumatology, Zao Zhuang Hospitai of Zao Zhuang Mining Group, Shandong, Zaozhuang, China

    Yan Chen

  3. Department of Orthopedics, Taihe Hospital, Hubei University of Medicine, No.32, South Renmin Road, Shiyan, 442000, Hubei, China

    Yunxiang Yu

  4. Department of Orthopedics, Taihe Hospital, Hubei University of Medicine, No.32, South Renmin Road, Hubei, 442000, Shiyan, China

    Yunxiang Yu

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  1. Jinying Hao
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Contributions

Jinying Hao designed the study and wrote the manuscript. Yan Chen analyzed the data and performed the experiments. Yunxiang Yu summarized the data. All authors contributed to this study, read and approved the manuscript.

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Correspondence to Yunxiang Yu.

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This study was approved by the Research Ethics Committee of Heping Hospital Affiliated to Changzhi Medical College. Informed consent was obtained.

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Highlights

1. Circ_0008360 was downregulated in RA synovial tissues and RA-FLSs.

2. Circ_0008360 inhibited the proliferation, migration and inflammation and promoted apoptosis of RA-FLSs by sponging miR-135b-5p.

3. MiR-135b-5p promoted the proliferation, migration and inflammation and inhibited apoptosis of RA-FLSs by targeting HDAC4.

4. Circ_0008360 regulated HDAC4 expression by acting as a sponge of miR-135b-5p.

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Hao, J., Chen, Y. & Yu, Y. Circular RNA circ_0008360 Inhibits the Proliferation, Migration, and Inflammation and Promotes Apoptosis of Fibroblast-Like Synoviocytes by Regulating miR-135b-5p/HDAC4 Axis in Rheumatoid Arthritis. Inflammation 45, 196–211 (2022). https://doi.org/10.1007/s10753-021-01538-4

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  • DOI: https://doi.org/10.1007/s10753-021-01538-4

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