# The Clinical Role of SRSF1 Expression in Cancer: A Review of the Current Literature
## 3 Results
### Review
#### 3.2.3 Lung Cancer  
Valid literature concerning the clinical role of SRSF1 in lung cancer started in 2010, when [PERSON] et al. observed its key role in NSCLS (non-small cell lung cancer) through an mTOR-dependent mechanism; the activation of the translational repressor 4E-BP1 and the activation of the surviving pathway seems to contribute to NSCLC progression [30]. Another in vitro study with cell culture of NSCLC and RNA transfection showed the role of Caspase 9 in chemotherapeutic sensitivity of non-small cell lung cancer; in particular, an alternative splicing event of Caspase 9, switching the expression ratio of Caspase 9a/9b from 9a to 9b, caused an increasing of resistance from cisplatinum, daunorubicin and paclitaxel. This study also demonstrated that the mutation of the C9-I6/ISE enhancer element, leading to the overexpression of Caspase 9b, is mediated by the interaction of SRSF1 with C9-I6/ISE; therefore, the in vitro study postulated that SRSF1 could be a lung cancer chemoresistance mediator [31]. Figure 3: SRSF1 role and pathways in breast 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. In 2012 [PERSON] et al. published a paper on tissue samples from 53 lung SCCs (squamous cell carcinoma) and 54 ADCs (lung adenocarcinoma), 25 normal lung samples where included, the tissue samples underwent Immunohistochemistry analysis to explore the expression of SR Pre-mRNA splicing regulators and, in particular, of SRSF1. This study found that the overexpression of SRSF1 is associated with worse stage and diagnosis (III/IV) and with the presence of metastases (M+) only in NSCLC and, in particular, in ADC [32]. [PERSON] et al. [33] in 2016 published the first whole genomic and transcriptomic sequence from a Chinese population of 99 SCLCs (Small Cell Lung Carcinoma), correlating with clinical and survival data. This study was conducted by the application of Immunohistochemistry-tochemistry techniques; however, the finding of gain of copy number of SRSF1, and its correlation with poor survival rates in the population, led to a switch to a cell culture-study that confirmed that SRSF1 plays a key role in SCLC, too. They found that the overexpression of SRSF1 regulates the BCL2 pathway resulting in a lack of pro-apoptotic activity; furthermore, the knockdown of SRSF1 also caused an activation of caspase-3, similar to the cisplatin effect and the combination of SRSF1 knockdown and cisplatin caused a stronger caspase-3 activation than cisplatin alone. In this study it was found that SRSF1 can also play a key role in DNA-damaging signals in SCLC, in particular, suppressing PI3K/ AKT and MEK/ERK pathways. SRSF1 seems to be involved in lung cancer radio-sensitivity, too. In particular, a cell culture and in vivo animal study published in 2018 found that isoforms of PTPMT1 (short isoform and long isoform) could play a role in radio-resistance and sensitivity in lung cancer in mice. SRSF1 was proven to be able to regulate an alternative splicing of PTPMT1 promoting overexpression of long isoform of that protein that can reduce expression of MAPK and reduce the DNA-damage response to radiotherapy. This study also hypothesized SRSF1 in control of several other candidates involved in radio-sensitivity pathways [34]. In 2018 a paper published by [PERSON] et al. demonstrated that SRSF1 regulates translation and/or stability of DNA ligase 1 (LIG1) by a mechanism depending on the activation of mTOR [35]. LIG1 is a DNA repair gene, in this study the authors demonstrated that LIG1 is a marker for poor prognosis in NSCLC, in particular, the authors found a correlation with a shorter Disease Free Survival (DFS) and Overall Survival; furthermore, in the same study LIG1 was identified as an independent prognostic factor for NSCLC [35]. A whole-transcriptome analysis was performed in 2019 from samples of lung cancer (LC) tissue and adjacent normal lung tissue to find AS events.