Search

Small nuclear ribonucleoprotein Sm D1 (SNRPD1), one of the crucial genes encoding core spliceosome components, was abnormally highly expressed in multiple types of tumors. In this study, we investigated the diagnostic and prognostic significance of SNRPD1 in hepatocellular carcinoma (HCC). The investigation of datasets from GEO and TCGA databases revealed that SNRPD1 expression in HCC was significantly higher than adjacent normal liver tissues, which was validated by immunohistochemistry (IHC). Both GO, KEGG analysis showed that the SNRPD1 co-expressed genes mainly enriched in Cell division, Nuclear import, mRNA splicing via spliceosome, Ribosome, Cell cycle, etc. Survival analysis from the GSE14520 dataset and 154 HCC cohorts exhibited a significant association of high SNRPD1 expression with poor overall survival and recurrence-free survival. ROC analysis showed that the abnormally high SNRPD1 mRNA expression has diagnostic significance in distinguishing between HCC and normal liver tissue (AUC = 0.819). Gene set enrichment analysis (GSEA) demonstrated that the high expression of SNRPD1 might regulate HCC tumorigenesis and progression by affecting the cell cycle, mismatch repair, DNA replication, and RNA degradation, etc. The luciferase report assay revealed that SNRPD1 was the direct target gene of miR-100 manifested by decreased SNRPD1 expression and luciferase activity in the HCC cells upon miR-100 overexpression. Finally, SNRPD1 may as an oncogene affecting the progression of HCC through regulates the mTOR pathway and autophagy.

Background SNRPD1 is a spliceosome-associated protein and has previously been implicated with important roles in cancer development. Methods Through analyzing the differential expression patterns and clinical association of splicing associated genes among tumor and tumor adjacent samples across different tumors and among different breast cancer subtypes, we identify the tumor promotive role of SNRPD1 using multiple publicly available datasets. Through pathway, gene ontology enrichment analysis and network construction, we linked the onco-therapeutic role of SNRPD1 with cell cycle. Via a series of experimental studies including knockdown assay, qPCR, western blotting, cell cycle, drug response assay, we confirmed the higher expression of SNPRD1 at both gene and protein expression levels in triple negative breast cancer cells, as well as its roles in promoting cell cycle and chemotherapy response. Results Our study revealed that SNRPD1 over-expression was significantly associated with genes involved in cell cycle, cell mitosis and chromatin replication, and silencing SNRPD1 in breast cancer cells could lead to halted tumor cell growth and cell cycle arrest at the G0/G1 stage. We also found that triple negative breast cancer cells with reduced SNRPD1 expression lost certain sensitivity to doxorubicin whereas luminal cancer cells did not. Conclusions Our results suggested the prognostic value of SNRPD1 on breast cancer survival, its potential as the therapeutic target halting cell cycle progression for breast cancer control, and warranted special attention on the combined use of doxorubicin and drugs targeting SNRPD1.