# The Clinical Role of SRSF1 Expression in Cancer: A Review of the Current Literature
###### Abstract  
Background: SFRS1 is a member of the splicing factor protein family. Through a specific sequence of alteration, SRSF1 can move from the cytoplasm to the nucleus where it can work autonomously as a splicing activator, or as a silencer when interacting with other regulators. Alternative splicing (AS) is a fundamental biological process that ensures protein diversity. In fact, different proteins, produced by alternative splicing, can gain different and even antagonistic biological functions. Methods: Our review is based on English articles published in the MEDLINE/PubMed Medical library between 2000 and 2021. We retrieved articles that were specifically related to SRSF1 and cancers, and we excluded other reviews and meta-analyses. We included in vitro studies, animal studies and clinical studies, evaluated using the Medical Education Research Study Quality Instrument (MERSQ) and the Newcastle-Ottawa Scale-Education (NOSE). **Result**: SRSF1 is related to various genes and plays a role in cell cycle, ubiquitin-mediated proteolysis, nucleotide excision repair, p53 pathway, apoptosis, DNA replication and RNA degradation. In most cases, SRSF1 carries out its cancer-related function via abnormal alternative splicing (AS). However, according to the most recent literature, SRSF1 may also be involved in mRNA translation and cancer chemoresistance or radio-sensitivity. Conclusion: Our results showed that SRSF1 plays a key clinical role in tumorigenesis and tumor progression in several types of cancer (such as Prostate, Lung, Breast, Colon, Glioblastoma), through various mechanisms of action and different cellular pathways. This review could be a starting point for several studies regarding the biology of and therapies for cancer. SRSF1; prostate; glioblastoma; lung; colon; breast; cancer; splicing +
Footnote †: journal: Medical and Surgical Sciences  
(SR protein-specific-kinase 1) on a precise serine residue contained in the SR domain [4]; due to its hypophosphorylation and through its association with a specific transportin, the protein is imported into nuclear storage. Therefore, SRSF1 recruitment to active sites of transcription, where it is involved in splicing regulation, requires a second phosphorylation, which is carried out by CLK (CDC-like kinase 1) [5; 6]. Therefore, SRSF1, bound to spliced-mRNA, is exported into the cytoplasm through its interaction with the TAP/NXF1 receptor [7]; this evidence is shown in Figure 1.  
Alternative splicing is a fundamental biological process that ensures protein diversity. In fact, different proteins, produced by alternative splicing, can gain different, and even antagonistic, biological functions. As a confirmation of this, through alternative splicing, about 95% of the human genome produces multiple mRNA transcripts by the differential inclusion or exclusion of exons [6]. There is much evidence of an association between alternative splicing and cancer insurance. Interesting, many genes involved in proliferation, invasiveness, and programmed cell death are modulated by alternative splicing and, as a consequence of failure to accurately recognize the splicing site, may generate mRNA variants encoding for deleterious protein-isoforms that contribute to tumor phenotypes [8; 9]. Some of these mutations are caused by changes that occurred at the splicing site of tumor-suppressor genes, while others are caused by alterations in splicing factor proteins [10]. Furthermore, according to the study conducted by [PERSON] et al., SRSF1, primarily driven by the hyperactivation of the transcription factor MYC, is overexpressed in a wide range of cancers and plays oncogenic roles through  
Figure 1: Alternative splicing event mediated by SRSF1. Created with Biorender. its control of AS of cancer related genes [11]. Moreover, changes in the expression of SRSF1 are potentially involved in splicing misregulation in several diseases including Retinitis Pigmentosa 4 and Homocystinuria [12].