# The Clinical Role of SRSF1 Expression in Cancer: A Review of the Current Literature
## 3 Results
### Review
#### 3.2.4 Colorectal Cancer  
A particularly important study was published in 2017 regarding the biological role of SRSF1 in colorectal cancer. A bioinformatics analysis was performed and the authors of this paper found that SRSF1 is related to several genes involved in colorectal cancer development and, in particular, they play a role in the cell cycle, such as in spliceosome, ubiquitin-mediated proteolysis, nucleotide excision repair, p53 pathway, DNA replication and RNA degradation. Further analysis found that SRSF1 is overexpressed in several types of colorectal cancer with a higher concentration in neoplastic tissue rather than in healthy tissue. A total of 468 SRSF1-related genes were found to be involved in colorectal cancers by overlapping 2678 SRSF1-related genes and 3625 colorectal cancer-related genes [45].  
Another study, performed in vitro and in vivo with a xenograft model in mice and also a clinical study, were published in 2017 and found several relationships between SRSF1 and colon cancer [46]. They investigated the role of AS events for the DBF4B subunit (DBF4 zinc finger B) of the cyclin Cdc7 Kinase that regulates DNA replication during the cell cycle. The expression of DBF4B is regulated during the cell cycle and in particular its  
Figure 4: SRSF1 role and pathways in lung cancer. Evidence from in vitro, animal or clinical studies are specified with pictures. Created with Biorender.  
inhibition results in the attenuation of cell growth and the expression of markers of DNA damage; DBF4B mRNA levels are high during the S phase of the cell cycle and low during the G1 phase [47]. The authors of this paper found that SRSF1 regulates, through AS, the inclusion of exon 6 in DBF4B (DBF4B-FL). To investigate the role of SRSF1 and DBF4B-FL in tumorigenesis in vivo, a xenograft model in mice with colon cancer cells (RKO) was performed; in particular, shRNAs targeted against DBF4B-FL and SRSF1 were introduced to knock them down in RKO cells and RKO/shDBF4B-FL and RKO/shSRSF1 were used to perform a xenograft. Both tests showed that DBF4B-FL and SRSF1 KD lead to a significant inhibition of cell growth.  
To investigate the clinical role of DBF4B-FL in colon cancer, the authors compared the ratio of DBF4B FL/S mRNA in clinical CRC samples, examining sixty human CRC tissues paired with their noncancerous tissues. Furthermore, both SRSF1 and DBF4B-FL were highly expressed in neoplastic cells with respect to noncancerous tissue. The authors then investigated the expression of SRSF1 and its AS product in colon cancer cells. They found that the expression of SRSF1/DBF4B-FL was correlated to higher tumor grade and, furthermore, at the Kaplan-Meier analysis and Cox regression SRSF1 and DBF4B-FL were related to worse survival rates and where also both independent prognostic factors for colon cancer [46].  
Comparable results with the previous work were found in 2021 in a study that confirmed SRSF1 as an independent prognostic factor in colorectal cancer, the same as the TNM classification. These results were also related to SRSF1 as an alternative splicing factor involved in the regulation of events such as MAPK interacting with Mnk2 (serine/threonine protein kinase 2), encoded by the MKNK2 gene. This protein plays a critical role in the MAPK pathway and can enhance tumorigenesis and proliferation [48].  
We can affirm that SRSF1 also plays an important clinical role in the prognosis and tumor development for colon cancer.  
This evidence is summarized in Figure 5.  
Figure 5: SRSF1 role and pathways in colorectal cancer. Evidence from in vitro, animal or clinical studies are specified with pictures. Created with Biorender. The Kaplan–Meier curves have only a figurative purpose.