Alternative splicing of EZH2 regulated by SNRPB mediates hepatocellular carcinoma progression via BMP2 signaling pathway
Summary: Increasing evidence suggests that aberrant alternative splicing plays crucial roles in tumorigenesis. However, the function of EZH2 splice variants as well as the mechanism by which EZH2 alternative splicing occurs in hepatocellular carcinoma (HCC) remain elusive. Here, we analyzed both our...
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Elsevier
2025-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224028530 |
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| author | Xingyu Wang Weiyi Liu Chunai Zhan Yuanyuan Zhang Xinyu Li Yaoyun Wang Mengfei Sheng Madiha Maqsood Hang Shen Anmin Liang Wei Shao |
| author_facet | Xingyu Wang Weiyi Liu Chunai Zhan Yuanyuan Zhang Xinyu Li Yaoyun Wang Mengfei Sheng Madiha Maqsood Hang Shen Anmin Liang Wei Shao |
| author_sort | Xingyu Wang |
| collection | DOAJ |
| description | Summary: Increasing evidence suggests that aberrant alternative splicing plays crucial roles in tumorigenesis. However, the function of EZH2 splice variants as well as the mechanism by which EZH2 alternative splicing occurs in hepatocellular carcinoma (HCC) remain elusive. Here, we analyzed both our own and published transcriptomic data, obtaining 19 splice variants of EZH2 in addition to canonical full-length EZH2-A in HCC. We found that expression of EZH2-A/EZH2-B in tumor tissues and cell lines was significantly higher than in normal tissues. Conversely, EZH2-C expression was lower in tumor tissues and cell lines than in normal tissues. Further functional analysis indicated that unlike full-length EZH2-A that promotes H3K27 methylation, EZH2-C reduced H3K27me3 levels. EZH2-C inhibited proliferation, migration, invasion of HCC cells. Moreover, EZH2-A and EZH2-C regulate the BMP2 signaling pathway oppositely. Mechanistically, EZH2’s alternative splicing was mediated by splicing factor SNRPB. In summary, this study revealed that alternative splicing of EZH2 regulates HCC. |
| format | Article |
| id | doaj-art-3cbfd5b438b442109b6ccf17ee4ee3a5 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-3cbfd5b438b442109b6ccf17ee4ee3a52025-01-03T04:08:53ZengElsevieriScience2589-00422025-01-01281111626Alternative splicing of EZH2 regulated by SNRPB mediates hepatocellular carcinoma progression via BMP2 signaling pathwayXingyu Wang0Weiyi Liu1Chunai Zhan2Yuanyuan Zhang3Xinyu Li4Yaoyun Wang5Mengfei Sheng6Madiha Maqsood7Hang Shen8Anmin Liang9Wei Shao10Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, ChinaDepartment of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, ChinaDepartment of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, ChinaDepartment of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, ChinaDepartment of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, ChinaDepartment of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, ChinaDepartment of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, ChinaDepartment of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, ChinaDepartment of Hepatopancreatobiliary Surgery, the First Affiliated Hospital, Anhui Medical University, Hefei 230000, ChinaCollege of Life Science, Wuhan University, Wuhan, Hubei 430072, ChinaDepartment of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, China; Corresponding authorSummary: Increasing evidence suggests that aberrant alternative splicing plays crucial roles in tumorigenesis. However, the function of EZH2 splice variants as well as the mechanism by which EZH2 alternative splicing occurs in hepatocellular carcinoma (HCC) remain elusive. Here, we analyzed both our own and published transcriptomic data, obtaining 19 splice variants of EZH2 in addition to canonical full-length EZH2-A in HCC. We found that expression of EZH2-A/EZH2-B in tumor tissues and cell lines was significantly higher than in normal tissues. Conversely, EZH2-C expression was lower in tumor tissues and cell lines than in normal tissues. Further functional analysis indicated that unlike full-length EZH2-A that promotes H3K27 methylation, EZH2-C reduced H3K27me3 levels. EZH2-C inhibited proliferation, migration, invasion of HCC cells. Moreover, EZH2-A and EZH2-C regulate the BMP2 signaling pathway oppositely. Mechanistically, EZH2’s alternative splicing was mediated by splicing factor SNRPB. In summary, this study revealed that alternative splicing of EZH2 regulates HCC.http://www.sciencedirect.com/science/article/pii/S2589004224028530Biological sciencesMolecular biologyMolecular mechanism of gene regulationCancer |
| spellingShingle | Xingyu Wang Weiyi Liu Chunai Zhan Yuanyuan Zhang Xinyu Li Yaoyun Wang Mengfei Sheng Madiha Maqsood Hang Shen Anmin Liang Wei Shao Alternative splicing of EZH2 regulated by SNRPB mediates hepatocellular carcinoma progression via BMP2 signaling pathway iScience Biological sciences Molecular biology Molecular mechanism of gene regulation Cancer |
| title | Alternative splicing of EZH2 regulated by SNRPB mediates hepatocellular carcinoma progression via BMP2 signaling pathway |
| title_full | Alternative splicing of EZH2 regulated by SNRPB mediates hepatocellular carcinoma progression via BMP2 signaling pathway |
| title_fullStr | Alternative splicing of EZH2 regulated by SNRPB mediates hepatocellular carcinoma progression via BMP2 signaling pathway |
| title_full_unstemmed | Alternative splicing of EZH2 regulated by SNRPB mediates hepatocellular carcinoma progression via BMP2 signaling pathway |
| title_short | Alternative splicing of EZH2 regulated by SNRPB mediates hepatocellular carcinoma progression via BMP2 signaling pathway |
| title_sort | alternative splicing of ezh2 regulated by snrpb mediates hepatocellular carcinoma progression via bmp2 signaling pathway |
| topic | Biological sciences Molecular biology Molecular mechanism of gene regulation Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224028530 |
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