背景:剪接事件失调是癌症中的常见现象,富含丝氨酸-精氨酸的剪接因子(SRSF)家族正在成为基因表达的关键调节因子,影响本构和替代拼接过程。尽管一些SRSF家族成员的畸变与各种癌症有关,其他家庭成分的综合作用仍未得到充分开发。
方法:本研究使用定量实时PCR方法深入研究了来自不同组织的23种癌细胞系中整个SRSF家族(SRSF1-SRSF12)的表达谱。Further,在分层为癌前期的口腔癌患者样本中检查了SRSF家族的转录水平(n=15),早期癌症(n=11),晚期癌症(n=14),和邻近的非肿瘤组织(n=26)作为对照。利用癌症基因组图谱(TCGA)数据库中提供的口腔鳞状细胞癌(OSCC)患者(n=319)和对照(n=35)的转录组学数据进行的平行研究证实了结果。
结果:我们的研究显示关键剪接因子的表达水平显著上调,即所有口腔癌细胞系(SCC-4、UM-SCC-84、CAL33、SAS-H1)中的SRSF3、SRSF9和SRSF10。相反,没有发现SRSF家族成员和其他癌细胞系之间的显著关联.Further,SRSF家族在口腔癌患者样本中的表达谱显示,与对照组相比,晚期口腔癌患者的SRSF1,SRSF3,SRSF7,SRSF9,SRSF10和SRSF11显著上调.TCGA数据库的转录组学数据显示,OSCC患者中SRSF1、SRSF4、SRSF9、SRSF10和SRSF11显著上调。
结论:我们的结果共同强调了SRSF家族成员在口腔癌中的重要参与,强调他们作为与癌症进展相关的剪接动力学改变的关键参与者的潜力。
BACKGROUND: Dysregulated splicing events are a common phenomenon in cancer with the Serine-arginine-rich splicing factor (SRSF) family emerging as pivotal regulators of gene expression, exerting influence over constitutive and alternative splicing processes. Although aberrations in a few SRSF family members have been implicated in various cancers, the comprehensive roles of other family constituents remain underexplored.
METHODS: This study delves into the expression profile of the entire SRSF family (SRSF1-SRSF12) in 23 cancerous cell lines originating from diverse tissues using quantitative Real-Time PCR. Further, the transcript levels of the SRSF family were examined in oral cancer patient samples stratified into Pre-cancer (n = 15), Early cancer (n = 11), Late cancer (n = 14), and adjacent non-tumor tissues (n = 26) as controls. The results were corroborated by a parallel investigation utilizing the transcriptomics data of oral squamous cell carcinoma (OSCC) patients (n = 319) and controls (n = 35) available in The Cancer Genome Atlas (TCGA) database.
RESULTS: Our investigation reveals a notable upregulation in the expression levels of key splicing factors, namely SRSF3, SRSF9, and SRSF10 in all oral cancer cell lines (SCC-4, UM-SCC-84, CAL33, SAS-H1). Conversely, no significant associations between SRSF family members and other cancer cell lines were discerned. Further, the expression profile of the SRSF family in oral cancer patient samples revealed significant upregulation of SRSF1, SRSF3, SRSF7, SRSF9, SRSF10, and SRSF11 in patients with late-stage oral cancer compared to controls. Transcriptomics data from TCGA database demonstrated remarkable upregulation of SRSF1, SRSF4, SRSF9, SRSF10, and SRSF11 in OSCC patients.
CONCLUSIONS: Collectively our results underscore the critical involvement of SRSF family members in the context of oral cancer, highlighting their potential as key players in the altered splicing dynamics associated with cancer progression.