Identification of signature mRNA candidates modulating chemoresistance of Oral squamous cell carcinoma

Abstract

Platinum drugs are well-known chemotherapeutic agents used for the treatment of numerous cancer types including OSCC. However, acquired resistance to platinum drugs makes complication in cancer chemotherapy and exhibit poor therapeutic outcomes. A growing number of evidence showed that dysregulation in drug uptake, DNA damage repair, apoptosis, autophagy, drug metabolism, EMT, etc. helps cancer cells to become resistant to chemotherapy. There are a couple of genes that are responsible for regulating such alterations within cancer cells to make them resistant. To date, not many studies have been done to found out a gene signature that collectively regulates most of the drug resistance-related events. In our study, we aimed to identify a candidate gene signature that will comprehensively regulate the drug resistance events in OSCC. Hence, we extracted potential genes by data mining from various data sources and literature, which are reported to be involved in platinum resistance in various cancers. First, we retrieved the genes from various literature and data sources that are involved in drug resistance in cancer. By categorizing these genes, we obtained mostly that they were involved in drug resistance by modulating drug export, apoptosis, drug-induced DNA damage repair, drug metabolism, and epithelial to mesenchymal transition EMT. Out of which we identified KLF5 as the most relevant gene imparting chemoresistance by altering DNA damage repair, apoptosis, and EMT. Our qRTPCR result shows the downregulated expression of KLF5 in cisplatin resistant SCC9 cell lines. So, by taking this we were working to identify the mechanism behind the downregulation of KLF5 in OSCC and its effect on the chemoresistance of chemo resistant OSCC cell lines. This study will help to establish KLF5 as a suitable candidate for overcoming chemoresistance-related complications in OSCC.