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Colorectal cancer (CRC) caused more than 65,000 mortalities worldwide per year. It is a result of one or a combination of chromosomal instability, CpG island methylator phenotype, and microsatellite instability. SNRPA1 (small nuclear ribonucleoprotein polypeptide A) is a subunit of spliceosome complex that is involved in the RNA processing. Overexpression of SNRPA1 has been implicated in a variety of cancers including CRC. Besides from its role in mediating the RNA processing, the other aspects regarding its function in the progression of colorectal cancer have not been revealed. Herein, we combined regular gene overexpression or knock down in vitro and in vivo and microarray gene profiling analysis to decipher the unknow regulatory role of SNRPA1 in CRC. We found SNRPA1 widely expression in many representative CRC cell lines. Knocking down expression of SNRPA1 by shRNA lentivirus inhibited the cell proliferation in vitro and impaired tumor formation from implanted CRC cells transduced with SNRPA1 silencing shRNA lentivirus in nude mice. It also promoted the cell apoptosis by upregulating the caspase 3/7 activity. Additional microarray gene profiling analysis uncovered the gene interaction network of SNRPA1 , special focus was placed on its association with tumor suppressor or oncogenes. According to the results of gene interaction network as well as qRT-PCR verification, it revealed that SNPRA1 regulates PIK3R1, VEGFC, MKI67, CDK1 in CRC. These novel findings identified new roles played by SNRPA1 in the progression of CRC and it may become a potential therapeutic target in the treatment of CRC. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Although adjuvant chemotherapy (ACT) is widely used to treat patients with Stage II/III colorectal cancer (CRC), administering ACT to specific patients remains a challenge. The decision to ACT requires an accurate assessment of recurrence risk and absolute treatment benefit. However, the traditional TNM staging system does not accurately assess a patient's individual risk of recurrence.To identify recurrence risk‐related genetic factors for Stage II/III CRC patients after radical surgery, we conducted an analysis of whole‐exome sequencing of 47 patients with Stage II/III CRC who underwent radical surgery at five institutions. Patients were grouped into non‐recurrence group (NR, n = 24, recurrence‐free survival [RFS] > 5 years) and recurrence group (R, n = 23, RFS <2 years). The TCGA‐COAD/READ cohort was employed as the validation dataset.A recurrence‐predictive model (G8plus score) based on eight gene (CUL9, PCDHA12, HECTD3, DCX, SMARCA2, FAM193A, AATK, and SORCS2) mutations and tumor mutation burden/microsatellite instability (TMB/MSI) status was constructed, with 97.87% accuracy in our data and 100% negative predictive value in the TCGA‐COAD/READ cohort. For the TCGA‐COAD/READ cohort, the G8plus‐high group had better RFS (HR = 0.22, p = 0.024); the G8plus‐high tumors had significantly more infiltrated immune cell types, higher tertiary lymphoid structure signature scores, and higher immunological signature scores. The G8plus score was also a predict biomarker for immunotherapeutic in advanced CRC in the PUCH cohort.In conclusion, the G8plus score is a powerful biomarker for predicting the risk of recurrence in patients with stage II/III CRC. It can be used to stratify patients who benefit from ACT and immunotherapy. [ABSTRACT FROM AUTHOR]