Human single-stranded DNA protein 1 (hSSB1): a new prognostic tool and target for non-small cell lung cancer treatment

Abstract

Introduction: Lung cancer is the leading cause of all cancer death worldwide. It is characterized by genomic instability leading to tissue invasion, metastasis and resistance to chemotherapy, notably cisplatin. Being the protein guardian of the genome, hSSB1 has a key role in the detection and repair of DNA damage (double-strand breaks, replication fork arrest and oxidative stress). Recently we have shown that hSSB1 is phosphorylated by DNA-PK at serine residue 134 in response to replication stress to promote cellular survival. We wanted to check is hSSB1 could be involved in the mechanism of non-small cell lung cancer (NSCLC) proliferation, establishing hSSB1 not only as a novel prognostic factor for NSCLC but also as a potential target for a new therapy strategy. Methods: We analyzed the prognostic significance of hSSB1 mRNA expression from public on line database and from protein expression in an NSCLC tissue macro-array (TMA) through hSSB1 immunohistochemistry staining. hSSB1 mRNA levels were analyzed in matched normal, tumour adenocarcinoma and squamous cell tumour samples. We explored the impact of hSSB1 expression on NSCLC cell lines proliferation by depleting hSSB1 with specific small interfering (si)RNA. We also measured the impact of hSSB1 inhibition on NSCLC cells proliferation with the use of a DNA-PK inhibitor. Results: hSSB1 expression was associated with poor prognosis for lung cancer, high levels of mRNA and protein expression correlating with a worse overall survival. We also observed that hSSB1 depletion leads to increased lung cancer cell death. The same result was observed when inhibiting hSSB1 by treating lung cancer cells with a DNA-PK inhibitor. Conclusion: Our results set hSSB1 as a prognostic factor in non-small cell lung cancer. Moreover, targeting hSSB1 proved to be effective to stop lung cancer cells proliferation, showing the potential as a new treatment for NSCLC. Disclosure: All authors have declared no conflicts of interest.