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Role of circular RNA cdr1as in modulation of macrophage phenotype
Gonzalez, Carolina Cimini, Maria Cheng, Zhongjian Wang, Chunlin Trungcao, May Mallaredy, Vandana Rajan, Sudarsan Garikipati, Venkata Naga Srikanth
Gonzalez, Carolina
Cimini, Maria
Cheng, Zhongjian
Wang, Chunlin
Trungcao, May
Mallaredy, Vandana
Rajan, Sudarsan
Garikipati, Venkata Naga Srikanth
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Journal article
Date
2022-10-01
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Cardiovascular Sciences
Medicine
Medicine
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http://dx.doi.org/10.1016/j.lfs.2022.121003
Abstract
Aims: Macrophages are crucial for the initiation and resolution of an inflammatory response. Non-coding circular RNAs are ubiquitously expressed in mammalian tissue, highly conserved among species, and recently implicated in the regulation of macrophage activation. We sought to determine whether circRNAs modulate monocyte/macrophage biology and function. Materials and Methods: We performed circRNA microarray analyses to assess transcriptome changes using RNA isolated from bone marrow derived macrophages polarized to a pro-inflammatory phenotype (INFγ + TNFα) or an anti-inflammatory phenotype (IL-10, IL-4, and TGF-β). Among differentially expressed circRNAs, circ-Cdr1as was chosen for further investigation. Additionally, we performed loss or gain of function studies to investigate if circ-Cdr1as is involved in phenotypic switching. For gain of function, we overexpressed circ-Cdr1as using pc3.1 plasmid with laccase2 flanking regions to promote circularization. For loss of function, we used a lentiviral short hairpin RNA targeting the circ-Cdr1as splicing junction. Key findings: Among circRNAs that are highly conserved and differentially expressed in pro- and anti-inflammatory lineages, circ-Cdr1as was one of the most downregulated in pro-inflammatory macrophages and significantly upregulated in anti-inflammatory macrophages in vitro. Overexpression of circ-Cdr1as increased transcription of anti-inflammatory markers and percentage of CD206+ cells in naïve and pro-inflammatory macrophages in vitro. Meanwhile, knockdown decreased transcription of anti-inflammatory markers and increased the percentage of CD86+ cells in naïve and anti-inflammatory macrophages in vitro. Significance: This study suggests that circ-Cdr1as plays a key role in regulating anti-inflammatory phenotype of macrophages and may potentially be developed as an anti-inflammatory regulator in tissue inflammation.
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Citation
Carolina Gonzalez, Maria Cimini, Zhongjian Cheng, Cindy Benedict, Chunlin Wang, May Trungcao, Vandana Mallaredy, Sudarsan Rajan, Venkata Naga Srikanth Garikipati, Raj Kishore, Role of circular RNA cdr1as in modulation of macrophage phenotype, Life Sciences, Volume 309, 2022, 121003, ISSN 0024-3205, https://doi.org/10.1016/j.lfs.2022.121003.
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Elsevier
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Life Sciences, Vol. 309
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