Temozolomide modulates the expression of miRNAs in colorectal cancer

Abstract

Cancer is the second leading cause of death globally, where nearly 1 in 6 deaths is due to cancer, with 70% of all deaths from cancer occur in low- and middle-income countries. The overall lifetime risk of developing colorectal cancer is 1 in 22 in men and 1 in 24 in women. In this work, we aimed to evaluate the role of temozolomide (TMZ) in controlling colon cancer cells (CRC) via regulating the miRnome. For this purpose, CRC cells (CaCo-2) were treated with 50 µM of TMZ for 48 h. Cell count using trypan test and cytotoxicity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) were carried out, and the obtained results indicated a significant decrease in cell count (p = 0.029), and in the cell viability (p = 0.0019). Cell cycle analysis was performed using flow cytometer, and results showed that TMZ arrested CRC cells at G2/M phase. A total of 84 miRNAs were profiled using real time PCR, and the results indicated that TMZ treatment upregulated 15 of 84 miRNAs panel profiled and downregulated the rest. The TMZ-upregulated/downregulated miRNAs were predicted to interact with many epigenetic-related proteins i.e., DNMTs, EZH2, and SUV31H1. This study shed some light on the role of TMZ in regulating the miRnome of CRC and hence in different types of cancers.

Keywords

• Temozolomide, CRC, CaCo-2, miRNA
• MiRnome, Epigenetics