Institute of Advanced Technology, Heilongjiang Academy of Sciences, Harbin, Heilongjiang, China.
Institute of Cancer Prevention and Treatment, Heilongjiang Province Academy of Medical Sciences, Harbin, Heilongjiang, China.
Technol Health Care. 2022;30(S1):293-301. doi: 10.3233/THC-THC228028.
Alternative splicing is a mechanism to produce different proteins with diverse functions from one gene. Many splicing factors play an important role in cancer progression. PRPF8 is a core protein component of the spliceosome complex, U4/U6-U5 tri-snRNP.
However, PRPF8 involved in mRNA alternative splicing are rarely included in the prognosis.
We found that PRPF8 was expressed in all examined cancer types. Further analyses found that PRPF8 expression was significantly different between the breast cancer and paracancerous tissues.
Survival analyses showed that PRPF8-high patients had a poor prognosis, and the expression of PRPF8 is associated with distant metastasis-free survival (DMFS) and post progression survival (PPS). Gene Set Enrichment Analysis (GSEA) has revealed that PRPF8 expression is correlated with TGF-β, JAK-STAT, and cell cycle control pathways. Consistent with these results, upon PRPF8 silencing, the growth of MCF-7 cells was reduced, the ability of cell clone formation was weakened, and p21 expression was increased.
These results have revealed that PRPF8 is a significant factor for splicing in breast cancer progression.
可变剪接是一种从一个基因产生具有不同功能的多种蛋白质的机制。许多剪接因子在癌症进展中发挥着重要作用。PRPF8 是剪接体复合物 U4/U6-U5 三 snRNP 的核心蛋白组成部分。
然而,参与 mRNA 可变剪接的 PRPF8 很少被包含在预后中。
我们发现 PRPF8 在所有检查的癌症类型中均有表达。进一步的分析发现,PRPF8 在乳腺癌和癌旁组织之间的表达存在显著差异。
生存分析表明 PRPF8 高表达的患者预后不良,PRPF8 的表达与无远处转移生存(DMFS)和进展后生存(PPS)相关。基因集富集分析(GSEA)表明 PRPF8 的表达与 TGF-β、JAK-STAT 和细胞周期控制途径相关。与这些结果一致的是,沉默 PRPF8 后,MCF-7 细胞的生长减少,细胞克隆形成能力减弱,p21 的表达增加。
这些结果表明 PRPF8 是乳腺癌进展中剪接的一个重要因素。