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| SCIN可变剪接在神经胶质瘤中的作用及机制研究 |
| The role and mechanism of Scinderin alternative splicing in Glioma |
| 投稿时间：2025-05-22 修订日期：2025-12-19 |
| DOI： |
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| 中文关键词: 神经胶质瘤细胞 SCIN 可变剪接 P53 |
| 英文关键词:Glioma SCIN Alternative splicing P53 |
| 基金项目:辽宁省教育厅科学技术研究项目（面上项目）（编号：JYTMS20231388）、辽宁省科技计划联合计划（自然科学基金-面上项目）（编号：2024-MSLH-458）、辽宁省科学技术计划（面上项目）（编号：2024-MS-224）、辽宁省科技计划联合计划（技术攻关计划项目）（编号：2024JH2/102600235）、沈阳医学院硕士研究生科技创新基金（编号：Y20240507） |
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| 中文摘要: |
| [目的]探究胶质瘤中SCIN的不同可变剪接形式对肿瘤细胞恶性生物学行为的影响及其相关分子机制。[方法]本研究通过Western blot方法检测不同肿瘤细胞系、神经胶质瘤不同细胞系、不同级别的神经胶质瘤组织中SCIN及其可变剪接的表达情况。运用CRISPR/Cas9技术建立SCIN敲除胶质瘤细胞模型,通过Westren blot检测其转染效率,采用CCK8、克隆形成法检测SCIN缺失后对人胶质瘤细胞增殖及克隆形成能力的影响,采用划痕实验、Transwell方法检测SCIN缺失后对人胶质瘤细胞迁移和侵袭的影响。通过质粒转染在基因敲除细胞模型中过表达SCIN不同可变剪接体,探究SCIN不同可变剪接对神经胶质瘤增殖、迁移、侵袭等恶行生物学行为的影响。通过Western blot检测SCIN及其可变剪接与P53的相关性。[结果]与对照组相比,SCIN缺失后,神经胶质瘤的增殖能力、克隆形成能力、迁移及侵袭能力均显著下降。468aa亚型异构蛋白可促进胶质瘤细胞迁移和侵袭等恶性生物学行为。P53缺失或异常可诱导SCIN可变剪接形成。[结论]原癌基因SCIN在神经胶质瘤中存在可变的剪接形式,其中468aa亚型异构蛋白异常高表达具有“促癌”作用；此外,SCIN的580aa剪接体的形成与P53蛋白的功能异常密切相关。 |
| 英文摘要: |
| [Objective] To investigate the impact of different alternative splicing forms of SCIN in glioma on the malignant biological behaviors of tumor cells and the related molecular mechanisms.[Methods] This study detected the expression of SCIN and its alternative splicing in different tumor cell lines, different glioma cell lines, and glioma tissues of various grades using the Western blot method. A SCIN knockout glioma cell model was established using CRISPR/Cas9 technology, and the transfection efficiency was verified by Western blot. The effects of SCIN deletion on the proliferation and clonogenic ability of human glioma cells were assessed using CCK8 and colony formation assays. The impact of SCIN deletion on the migration and invasion of human glioma cells was evaluated using scratch wound healing and Transwell assays. Different SCIN splice variants were overexpressed in the knockout cell model through plasmid transfection to explore the effects of various SCIN splice forms on the malignant biological behaviors of glioma, such as proliferation, migration, and invasion. The correlation between SCIN and its splice variants with P53 was examined by Western blot.[Results] Compared to the control group, the proliferation, clonogenic ability, migration, and invasion of glioma cells significantly decreased after SCIN deletion. The 468aa isoform promoted malignant biological behaviors such as migration and invasion in glioma cells. The absence or abnormality of P53 could induce the formation of SCIN alternative splicing.[Conclusion] In summary, the proto-oncogene SCIN has alternative splicing forms in glioma, with the aberrant high expression of the 468aa isoform exhibiting a "cancer-promoting" effect. Additionally, the formation of the 580aa splice variant of SCIN is closely related to the dysfunction of the P53 protein. |
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