NSUN2-mediated RNA m5C modification modulates uveal melanoma cell proliferation and migration
RNA 5-methylcytosine (m5C) is a widespread post-transcriptional modification involved in diverse biological processes through controlling RNA metabolism. However, its roles in uveal melanoma (UM) remain unknown. Here, we describe the biological roles and regulatory mechanisms of RNA m5C in UM. Initi...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-08-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2022.2088047 |
| _version_ | 1797678797058736128 |
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| author | Guangying Luo Weiwei Xu Xiaoyan Chen Siqi Wang Jiao Wang Feng Dong Dan-Ning Hu Peter S. Reinach Dongsheng Yan |
| author_facet | Guangying Luo Weiwei Xu Xiaoyan Chen Siqi Wang Jiao Wang Feng Dong Dan-Ning Hu Peter S. Reinach Dongsheng Yan |
| author_sort | Guangying Luo |
| collection | DOAJ |
| description | RNA 5-methylcytosine (m5C) is a widespread post-transcriptional modification involved in diverse biological processes through controlling RNA metabolism. However, its roles in uveal melanoma (UM) remain unknown. Here, we describe the biological roles and regulatory mechanisms of RNA m5C in UM. Initially, we identified significantly elevated global RNA m5C levels in both UM cells and tissue specimens using ELISA assay and dot blot analysis. Meanwhile, NOP2/Sun RNA methyltransferase family member 2 (NSUN2) was upregulated in both types of these samples, whereas NSUN2 knockdown significantly decreased RNA m5C level. Such declines inhibited UM cell migration and suppressed cell proliferation through cell cycle G1 arrest. Furthermore, bioinformatic analyses, m5C-RIP-qPCR, and luciferase assay identified β-Catenin (CTNNB1) as a direct target of NSUN2-mediated m5C modification in UM cells. Additionally, overexpression of miR-124a in UM cells diminished NSUN2 expression levels indicating that it is an upstream regulator of this response. Our study suggests that NSUN2-mediated RNA m5C methylation provides a potential novel target to improve the therapeutic management of UM pathogenesis. |
| first_indexed | 2024-03-11T23:05:09Z |
| format | Article |
| id | doaj.art-09adb7349e7b49c8ab239726e19811ed |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:05:09Z |
| publishDate | 2022-08-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-09adb7349e7b49c8ab239726e19811ed2023-09-21T13:23:12ZengTaylor & Francis GroupEpigenetics1559-22941559-23082022-08-0117892293310.1080/15592294.2022.20880472088047NSUN2-mediated RNA m5C modification modulates uveal melanoma cell proliferation and migrationGuangying Luo0Weiwei Xu1Xiaoyan Chen2Siqi Wang3Jiao Wang4Feng Dong5Dan-Ning Hu6Peter S. Reinach7Dongsheng Yan8Eye Hospital, Wenzhou Medical UniversityEye Hospital, Wenzhou Medical UniversityEye Hospital, Wenzhou Medical UniversityEye Hospital, Wenzhou Medical UniversityEye Hospital, Wenzhou Medical UniversityZhejiang UniversityOptometry and Visual ScienceEye Hospital, Wenzhou Medical UniversityEye Hospital, Wenzhou Medical UniversityRNA 5-methylcytosine (m5C) is a widespread post-transcriptional modification involved in diverse biological processes through controlling RNA metabolism. However, its roles in uveal melanoma (UM) remain unknown. Here, we describe the biological roles and regulatory mechanisms of RNA m5C in UM. Initially, we identified significantly elevated global RNA m5C levels in both UM cells and tissue specimens using ELISA assay and dot blot analysis. Meanwhile, NOP2/Sun RNA methyltransferase family member 2 (NSUN2) was upregulated in both types of these samples, whereas NSUN2 knockdown significantly decreased RNA m5C level. Such declines inhibited UM cell migration and suppressed cell proliferation through cell cycle G1 arrest. Furthermore, bioinformatic analyses, m5C-RIP-qPCR, and luciferase assay identified β-Catenin (CTNNB1) as a direct target of NSUN2-mediated m5C modification in UM cells. Additionally, overexpression of miR-124a in UM cells diminished NSUN2 expression levels indicating that it is an upstream regulator of this response. Our study suggests that NSUN2-mediated RNA m5C methylation provides a potential novel target to improve the therapeutic management of UM pathogenesis.http://dx.doi.org/10.1080/15592294.2022.2088047nsun2rna m5cuveal melanomacell proliferation and migrationctnnb1mir-124a |
| spellingShingle | Guangying Luo Weiwei Xu Xiaoyan Chen Siqi Wang Jiao Wang Feng Dong Dan-Ning Hu Peter S. Reinach Dongsheng Yan NSUN2-mediated RNA m5C modification modulates uveal melanoma cell proliferation and migration Epigenetics nsun2 rna m5c uveal melanoma cell proliferation and migration ctnnb1 mir-124a |
| title | NSUN2-mediated RNA m5C modification modulates uveal melanoma cell proliferation and migration |
| title_full | NSUN2-mediated RNA m5C modification modulates uveal melanoma cell proliferation and migration |
| title_fullStr | NSUN2-mediated RNA m5C modification modulates uveal melanoma cell proliferation and migration |
| title_full_unstemmed | NSUN2-mediated RNA m5C modification modulates uveal melanoma cell proliferation and migration |
| title_short | NSUN2-mediated RNA m5C modification modulates uveal melanoma cell proliferation and migration |
| title_sort | nsun2 mediated rna m5c modification modulates uveal melanoma cell proliferation and migration |
| topic | nsun2 rna m5c uveal melanoma cell proliferation and migration ctnnb1 mir-124a |
| url | http://dx.doi.org/10.1080/15592294.2022.2088047 |
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