Human lncRNA <i>SUGCT-AS1</i> Regulates the Proinflammatory Response of Macrophage
Macrophages are the major primary immune cells that mediate the inflammatory response. In this process, long non-coding RNAs (lncRNAs) play an important, yet largely unknown role. Therefore, utilizing several publicly available RNA sequencing datasets, we predicted and selected lncRNAs that are diff...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/17/13315 |
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| author | Yeong-Hwan Lim Gwangho Yoon Yeongseo Ryu Dahee Jeong Juhyun Song Yong Sook Kim Youngkeun Ahn Hyun Kook Young-Kook Kim |
| author_facet | Yeong-Hwan Lim Gwangho Yoon Yeongseo Ryu Dahee Jeong Juhyun Song Yong Sook Kim Youngkeun Ahn Hyun Kook Young-Kook Kim |
| author_sort | Yeong-Hwan Lim |
| collection | DOAJ |
| description | Macrophages are the major primary immune cells that mediate the inflammatory response. In this process, long non-coding RNAs (lncRNAs) play an important, yet largely unknown role. Therefore, utilizing several publicly available RNA sequencing datasets, we predicted and selected lncRNAs that are differentially expressed in M1 or M2 macrophages and involved in the inflammatory response. We identified <i>SUGCT-AS1</i>, which is a human macrophage-specific lncRNA whose expression is increased upon M1 macrophage stimulation. Conditioned media of <i>SUGCT-AS1</i>-depleted M1 macrophages induced an inflammatory phenotype of vascular smooth muscle cells, which included increased expression of inflammatory genes (<i>IL1B</i> and <i>IL6</i>), decreased contractile marker proteins (ACTA2 and SM22α), and increased cell migration. Depletion of <i>SUGCT-AS1</i> promoted the expression and secretion of proinflammatory cytokines, such as <i>TNF</i>, <i>IL1B</i>, and <i>IL6</i>, in M1 macrophages, and transcriptomic analysis showed that <i>SUGCT-AS1</i> has functions related to inflammatory responses and cytokines. Furthermore, we found that <i>SUGCT-AS1</i> directly binds to hnRNPU and regulates its nuclear–cytoplasmic translocation. This translocation of hnRNPU altered the proportion of the <i>MALT1</i> isoforms by regulating the alternative splicing of <i>MALT1</i>, a mediator of NF-κB signaling. Overall, our findings suggest that lncRNAs can be used for future studies on macrophage regulation. Moreover, they establish the <i>SUGCT-AS1</i>/hnRNPU/<i>MALT1</i> axis, which is a novel inflammatory regulatory mechanism in macrophages. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:21:53Z |
| publishDate | 2023-08-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cbe709ab29624df9ac782836659a6e5f2023-11-19T08:15:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171331510.3390/ijms241713315Human lncRNA <i>SUGCT-AS1</i> Regulates the Proinflammatory Response of MacrophageYeong-Hwan Lim0Gwangho Yoon1Yeongseo Ryu2Dahee Jeong3Juhyun Song4Yong Sook Kim5Youngkeun Ahn6Hyun Kook7Young-Kook Kim8Basic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Hwasun 58128, Republic of KoreaDivision of Brain Disease Research, Department for Chronic Disease Convergence Research, Korea National Institute of Health, Cheongju 28159, Republic of KoreaDepartment of Biochemistry, Chonnam National University Medical School, Hwasun 58128, Republic of KoreaDepartment of Biochemistry, Chonnam National University Medical School, Hwasun 58128, Republic of KoreaBioMedical Sciences Graduate Program (BMSGP), Chonnam National University, Hwasun 58128, Republic of KoreaBasic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Hwasun 58128, Republic of KoreaBasic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Hwasun 58128, Republic of KoreaBasic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Hwasun 58128, Republic of KoreaBasic Research Laboratory for Vascular Remodeling, Chonnam National University Medical School, Hwasun 58128, Republic of KoreaMacrophages are the major primary immune cells that mediate the inflammatory response. In this process, long non-coding RNAs (lncRNAs) play an important, yet largely unknown role. Therefore, utilizing several publicly available RNA sequencing datasets, we predicted and selected lncRNAs that are differentially expressed in M1 or M2 macrophages and involved in the inflammatory response. We identified <i>SUGCT-AS1</i>, which is a human macrophage-specific lncRNA whose expression is increased upon M1 macrophage stimulation. Conditioned media of <i>SUGCT-AS1</i>-depleted M1 macrophages induced an inflammatory phenotype of vascular smooth muscle cells, which included increased expression of inflammatory genes (<i>IL1B</i> and <i>IL6</i>), decreased contractile marker proteins (ACTA2 and SM22α), and increased cell migration. Depletion of <i>SUGCT-AS1</i> promoted the expression and secretion of proinflammatory cytokines, such as <i>TNF</i>, <i>IL1B</i>, and <i>IL6</i>, in M1 macrophages, and transcriptomic analysis showed that <i>SUGCT-AS1</i> has functions related to inflammatory responses and cytokines. Furthermore, we found that <i>SUGCT-AS1</i> directly binds to hnRNPU and regulates its nuclear–cytoplasmic translocation. This translocation of hnRNPU altered the proportion of the <i>MALT1</i> isoforms by regulating the alternative splicing of <i>MALT1</i>, a mediator of NF-κB signaling. Overall, our findings suggest that lncRNAs can be used for future studies on macrophage regulation. Moreover, they establish the <i>SUGCT-AS1</i>/hnRNPU/<i>MALT1</i> axis, which is a novel inflammatory regulatory mechanism in macrophages.https://www.mdpi.com/1422-0067/24/17/13315long non-coding RNAs<i>SUGCT-AS1</i>hnRNPU<i>MALT1</i>macrophagevascular smooth muscle cells |
| spellingShingle | Yeong-Hwan Lim Gwangho Yoon Yeongseo Ryu Dahee Jeong Juhyun Song Yong Sook Kim Youngkeun Ahn Hyun Kook Young-Kook Kim Human lncRNA <i>SUGCT-AS1</i> Regulates the Proinflammatory Response of Macrophage International Journal of Molecular Sciences long non-coding RNAs <i>SUGCT-AS1</i> hnRNPU <i>MALT1</i> macrophage vascular smooth muscle cells |
| title | Human lncRNA <i>SUGCT-AS1</i> Regulates the Proinflammatory Response of Macrophage |
| title_full | Human lncRNA <i>SUGCT-AS1</i> Regulates the Proinflammatory Response of Macrophage |
| title_fullStr | Human lncRNA <i>SUGCT-AS1</i> Regulates the Proinflammatory Response of Macrophage |
| title_full_unstemmed | Human lncRNA <i>SUGCT-AS1</i> Regulates the Proinflammatory Response of Macrophage |
| title_short | Human lncRNA <i>SUGCT-AS1</i> Regulates the Proinflammatory Response of Macrophage |
| title_sort | human lncrna i sugct as1 i regulates the proinflammatory response of macrophage |
| topic | long non-coding RNAs <i>SUGCT-AS1</i> hnRNPU <i>MALT1</i> macrophage vascular smooth muscle cells |
| url | https://www.mdpi.com/1422-0067/24/17/13315 |
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