RNA-binding proteins potentially regulate the alternative splicing of apoptotic genes during knee osteoarthritis progression
Abstract Background Alternative splicing (AS) is a principal mode of genetic regulation and one of the most widely used mechanisms to generate structurally and functionally distinct mRNA and protein variants. Dysregulation of AS may result in aberrant transcription and protein products, leading to t...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | BMC Genomics |
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| Online Access: | https://doi.org/10.1186/s12864-024-10181-w |
| _version_ | 1797247482506248192 |
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| author | Zheng Zhang Limei Dong Hai Tao Yusong Dong Wei Xiang Fenghua Tao Yingchun Zhao |
| author_facet | Zheng Zhang Limei Dong Hai Tao Yusong Dong Wei Xiang Fenghua Tao Yingchun Zhao |
| author_sort | Zheng Zhang |
| collection | DOAJ |
| description | Abstract Background Alternative splicing (AS) is a principal mode of genetic regulation and one of the most widely used mechanisms to generate structurally and functionally distinct mRNA and protein variants. Dysregulation of AS may result in aberrant transcription and protein products, leading to the emergence of human diseases. Although considered important for regulating gene expression, genome-wide AS dysregulation, underlying mechanisms, and clinical relevance in knee osteoarthritis (OA) remain unelucidated. Therefore, in this study, we elucidated and validated AS events and their regulatory mechanisms during OA progression. Results In this study, we identified differentially expressed genes between human OA and healthy meniscus samples. Among them, the OA-associated genes were primarily enriched in biological pathways such as extracellular matrix organization and ossification. The predominant OA-associated regulated AS (RAS) events were found to be involved in apoptosis during OA development. The expression of the apoptosis-related gene BCL2L13, XAF1, and NF2 were significantly different between OA and healthy meniscus samples. The construction of a covariation network of RNA-binding proteins (RBPs) and RAS genes revealed that differentially expressed RBP genes LAMA2 and CUL4B may regulate the apoptotic genes XAF1 and BCL2L13 to undergo AS events during OA progression. Finally, RT-qPCR revealed that CUL4B expression was significantly higher in OA meniscus samples than in normal controls and that the AS ratio of XAF1 was significantly different between control and OA samples; these findings were consistent with their expected expression and regulatory relationships. Conclusions Differentially expressed RBPs may regulate the AS of apoptotic genes during knee OA progression. XAF1 and its regulator, CUL4B, may serve as novel biomarkers and potential therapeutic targets for this disease. |
| first_indexed | 2024-04-24T19:59:24Z |
| format | Article |
| id | doaj.art-91913380435c4f329168b2c6020c5918 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-04-24T19:59:24Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-91913380435c4f329168b2c6020c59182024-03-24T12:11:17ZengBMCBMC Genomics1471-21642024-03-0125111310.1186/s12864-024-10181-wRNA-binding proteins potentially regulate the alternative splicing of apoptotic genes during knee osteoarthritis progressionZheng Zhang0Limei Dong1Hai Tao2Yusong Dong3Wei Xiang4Fenghua Tao5Yingchun Zhao6Department of Orthopedics, Renmin Hospital of Wuhan UniversitySchool of Basic Medical Sciences, Wuhan UniversityDepartment of Orthopedics, Renmin Hospital of Wuhan UniversitySchool of Basic Medical Sciences, Wuhan UniversityDepartment of Orthopedics, Renmin Hospital of Wuhan UniversityDepartment of Orthopedics, Renmin Hospital of Wuhan UniversityDepartment of Orthopedics, Renmin Hospital of Wuhan UniversityAbstract Background Alternative splicing (AS) is a principal mode of genetic regulation and one of the most widely used mechanisms to generate structurally and functionally distinct mRNA and protein variants. Dysregulation of AS may result in aberrant transcription and protein products, leading to the emergence of human diseases. Although considered important for regulating gene expression, genome-wide AS dysregulation, underlying mechanisms, and clinical relevance in knee osteoarthritis (OA) remain unelucidated. Therefore, in this study, we elucidated and validated AS events and their regulatory mechanisms during OA progression. Results In this study, we identified differentially expressed genes between human OA and healthy meniscus samples. Among them, the OA-associated genes were primarily enriched in biological pathways such as extracellular matrix organization and ossification. The predominant OA-associated regulated AS (RAS) events were found to be involved in apoptosis during OA development. The expression of the apoptosis-related gene BCL2L13, XAF1, and NF2 were significantly different between OA and healthy meniscus samples. The construction of a covariation network of RNA-binding proteins (RBPs) and RAS genes revealed that differentially expressed RBP genes LAMA2 and CUL4B may regulate the apoptotic genes XAF1 and BCL2L13 to undergo AS events during OA progression. Finally, RT-qPCR revealed that CUL4B expression was significantly higher in OA meniscus samples than in normal controls and that the AS ratio of XAF1 was significantly different between control and OA samples; these findings were consistent with their expected expression and regulatory relationships. Conclusions Differentially expressed RBPs may regulate the AS of apoptotic genes during knee OA progression. XAF1 and its regulator, CUL4B, may serve as novel biomarkers and potential therapeutic targets for this disease.https://doi.org/10.1186/s12864-024-10181-wKnee osteoarthritisRNA binding proteinAlternative splicingTranscriptomeDifferentially expressed genesApoptosis |
| spellingShingle | Zheng Zhang Limei Dong Hai Tao Yusong Dong Wei Xiang Fenghua Tao Yingchun Zhao RNA-binding proteins potentially regulate the alternative splicing of apoptotic genes during knee osteoarthritis progression BMC Genomics Knee osteoarthritis RNA binding protein Alternative splicing Transcriptome Differentially expressed genes Apoptosis |
| title | RNA-binding proteins potentially regulate the alternative splicing of apoptotic genes during knee osteoarthritis progression |
| title_full | RNA-binding proteins potentially regulate the alternative splicing of apoptotic genes during knee osteoarthritis progression |
| title_fullStr | RNA-binding proteins potentially regulate the alternative splicing of apoptotic genes during knee osteoarthritis progression |
| title_full_unstemmed | RNA-binding proteins potentially regulate the alternative splicing of apoptotic genes during knee osteoarthritis progression |
| title_short | RNA-binding proteins potentially regulate the alternative splicing of apoptotic genes during knee osteoarthritis progression |
| title_sort | rna binding proteins potentially regulate the alternative splicing of apoptotic genes during knee osteoarthritis progression |
| topic | Knee osteoarthritis RNA binding protein Alternative splicing Transcriptome Differentially expressed genes Apoptosis |
| url | https://doi.org/10.1186/s12864-024-10181-w |
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