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目的 探讨丝氨酸/精氨酸富集剪接因子 9(SRSF9)基因对乳腺癌增殖、迁移和侵袭的影响。方法 基于癌症基因组图谱(TCGA)数据库分析SRSF9基因在乳腺癌中表达情况,在乳腺癌细胞中分别构建SRSF9过表达和敲低模型,并使用Western blot进行验证。接着,通过一系列的体外细胞功能实验(克隆形成实验、CCK-8实验、Transwell实验和划痕愈合实验)探索敲低及过表达SRSF9基因对乳腺癌中增殖、迁移和侵袭的影响。结果 TCGA数据库分析结果显示SRSF9在乳腺癌组织中表达水平显著高于正常组织,且其高表达与乳腺癌患者较短的总生存期相关。在人乳腺癌细胞系MCF-7和MDA-MB-231中,SRSF9 敲低组蛋白表达水平降低,细胞克隆形成能力、增殖能力、迁移与侵袭能力较对照组显著降低,反之则增强。结论 SRSF9在乳腺癌中发挥促癌因子的作用,SRSF9的高表达不仅是乳腺癌预后不良的分子标志,还可能成为潜在的干预靶点。
Abstract:Objective To investigate the effect of the SRSF9 (serine/arginine-rich splicing factor 9) gene on the proliferation, migration, and invasion of breast cancer cells. Methods The expression of SRSF9 in breast cancer was analyzed using data from The Cancer Genome Atlas (TCGA) database. SRSF9 overexpression and knockdown models were constructed in breast cancer cell lines and validated using Western blot. Subsequently, a series of in vitro cellular functional assays (colony formation assay, CCK-8 assay, Transwell assay, wound healing assay) were conducted to explore the impact of SRSF9 knockdown and overexpression on the proliferation, migration, and invasion of breast cancer. Results Analysis of the TCGA database revealed that SRSF9 expression was significantly higher in breast cancer tissues compared to normal tissues, and high expression was associated with shorter overall survival. In human breast cancer cell lines MCF-7 and MDA-MB-231, the SRSF9 knockdown group showed reduced protein expression levels, and significantly decreased abilities in colony formation, proliferation, migration, and invasion compared to the control group. Conversely, these abilities were enhanced in the overexpression group. Conclusion SRSF9 acts as a pro-oncogenic factor in breast cancer, Its elevated expression not only serves as a molecular marker of poor prognosis but also represents a potential therapeutic target for intervention.
[1] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA A Cancer J Clin, 2024, 74(3): 229-63. doi:10.3322/caac.21834.
[2] Siegel R L, Kratzer T B, Giaquinto A N, et al. Cancer statistics, 2025[J]. CA A Cancer J Clin, 2025, 75(1): 10-45. doi:10.3322/caac.21871.
[3] Bakalis E, Ferraro A, Gavriil V, et al. Universal markers unveil metastatic cancerous cross-sections at nanoscale[J]. Cancers, 2022, 14(15): 3728. doi:10.3390/cancers14153728.
[4] Wang J, Wu SG. Breast cancer: an overview of current therapeutic strategies, challenge, and perspectives[J]. Breast Cancer (Dove Med Press), 2023, 15: 721-30. doi: 10.2147/BCTT.S432526.
[5] Lim B, Hortobagyi G N. Current challenges of metastatic breast cancer[J]. Cancer Metastasis Rev, 2016, 35(4): 495-514. doi:10.1007/s10555-016-9636-y.
[6] Bonnal S C, López-Oreja I, Valcárcel J. Roles and mechanisms of alternative splicing in cancer—implications for care[J]. Nat Rev Clin Oncol, 2020, 17(8): 457-74. doi:10.1038/s41571-020-0350-x.
[7] Zheng X, Peng Q, Wang L, et al. Serine/arginine-rich splicing factors: the bridge linking alternative splicing and cancer[J]. Int J Biol Sci, 2020, 16(13): 2442-53. doi:10.7150/ijbs.46751. [PubMed]
[8] Fu Y, Huang B, Shi Z, et al. SRSF1 and SRSF9 RNA binding proteins promote Wnt signalling-mediated tumorigenesis by enhancing β-catenin biosynthesis[J]. EMBO Mol Med, 2013, 5(5): 737-50. doi:10.1002/emmm.201202218.
[9] Li H, Shen S,et al. SRSF9 promotes tumor growth of non-small cell lung cancer cells by enhancing mTOR activity[J]. Oncogene. 2021, 40(7): 1282-94.
[10] Wang X, Lu X, Wang P, et al. SRSF9 promotes colorectal cancer progression via stabilizing DSN1 mRNA in an m6A-related manner[J]. J Transl Med, 2022, 20(1): 198. doi:10.1186/s12967-022-03399-3.
[11] 汪京京, 张真豪, 穆会君, 等. SRSF9基因敲除胶质母细胞瘤细胞株基因回补及其功能研究[J]. 安徽医科大学学报, 2021, 56(4): 550-5. doi:10.19405/j.cnki.issn1000-1492.2021.04.009.
[12] Shanmugam R, Zhang F, Srinivasan H, et al. SRSF9 selectively represses ADAR2-mediated editing of brain-specific sites in Primates[J]. Nucleic Acids Res, 2018, 46(14): 7379-95. doi:10.1093/nar/gky615.
[13] Somberg M, Li X, Johansson C, et al. Serine/arginine-rich protein 30c activates human papillomavirus type 16 L1 mRNA expression via a bimodal mechanism[J]. J Gen Virol, 2011, 92(Pt 10): 2411-21. doi:10.1099/vir.0.033183-0.
[14] Dastpak M, Mimoso C A, Farshchian M, et al. SF_(3)B_(1)K_(700)E mutation in human embryonic stem cells causes aberrant expression of immune-related genes[J]. PLoS One, 2025, 20(12): e0334361. doi:10.1371/journal.pone.0334361.
[15] Liu J, Wang Y, Yin J, et al. Pan-cancer analysis revealed SRSF9 as a new biomarker for prognosis and immunotherapy[J]. J Oncol, 2022, 2022: 3477148. doi:10.1155/2022/3477148.
基本信息:
中图分类号:R737.9
引用信息:
[1]王文娟,郭欠影,吴正升.SRSF9在乳腺癌中表达及其生物学功能[J].安徽医科大学学报().
基金信息:
国家自然科学基金项目(编号:82473059)
2026-08-26
2026-08-26
2026-08-26