Evaluation of miR-۱۰۷, DAPK۱, and KLF۴ Expression in Colorectal Tumors and Effect of Oxaliplatin and ۵-FU on their Levels in Colorectal Cancer Cell Lines

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-۱۰۷, Krüppel-like factor ۴ (KLF۴) and death-associated protein kinase (DAPK۱) genes in malignant and normal colon tissues and also colorectal cancer (CRC) model cells exposed to oxaliplatin and ۵-FU chemotherapy agents. Method: In this case-control study, the tissue samples from CRC patients were collected during colonoscopy process in ۲۰۱۳ -۲۰۱۶ at Imam Reza hospital. Subsequently, the expression levels of miR-۱۰۷, KLF۴, and DAPK۱ 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-۱۰۷, KLF۴ and DAPK۱ transcripts after oxaliplatin and ۵-FU treatment. Results: Unlike miR-۱۰۷, the expression levels of KLF۴ and DAPK۱ genes decreased in the tumor samples compared to those in the marginal specimens. In addition, both oxaliplatin and ۵-FU significantly increased the expression level of miR-۱۰۷. There were significant correlations between the expression levels of miR-۱۰۷, KLF۴, and DAPK۱genes and clinicopathological features, for instance lymph node metastasis and cell differentiation. Conclusion: The current study suggested a tumor suppressor role for KLF۴ and DAPK۱ in CRC. The altered expression of miR-۱۰۷, KLF-۴, and DAPK۱ 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.

Keywords:

Colorectal neoplasms , miR-۱۰۷ , KLF۴ , DAPK۱ , Oxaliplatin , ۵-Fu