Evaluation of miR-107, DAPK1, and KLF4 Expression in Colorectal Tumors and Effect of Oxaliplatin and 5-FU on their Levels in Colorectal Cancer Cell Lines

Abstract

Background: In recent years, the role of micro-RNAs in the cancer pathophysiology has attracted a great deal of scientific attention. MiRNAs regulate a variety of cellular functions, such as apoptosis, differentiation and migration by targeting oncogenic or tumor suppressor genes. We conducted the current study to assess the expression of miR-107, Kruppel-like factor 4 (KLF4) and death-associated protein kinase (DAPK1) genes in malignant and normal colon tissues and also colorectal cancer (CRC) model cells exposed to oxaliplatin and 5-FU chemotherapy agents. Method: In this case-control study, the tissue samples from CRC patients were collected during colonoscopy process in 2013 -2016 at Imam Reza hospital. Subsequently, the expression levels of miR-107, KLF4, and DAPK1 were detected with quantitative Real-Time PCR. Furthermore, in the in vitro phase of this study, we investigated the changes in the expression level of miR-107, KLF4 and DAPK1 transcripts after oxaliplatin and 5-FU treatment. Results: Unlike miR-107, the expression levels of KLF4 and DAPK1 genes decreased in the tumor samples compared to those in the marginal specimens. In addition, both oxaliplatin and 5-FU significantly increased the expression level of miR-107. There were significant correlations between the expression levels of miR-107, KLF4, and DAPK1genes and clinicopathological features, for instance lymph node metastasis and cell differentiation. Conclusion: The current study suggested a tumor suppressor role for KLF4 and DAPK1 in CRC. The altered expression of miR-107, KLF-4, and DAPK1 genes in CRC tumors and healthy tissues could be utilized for CRC diagnosis and prognosis. Furthermore, the studied genes could be considered as potential therapeutic targets in CRC.