J Cancer 2019; 10(18):4256-4263. doi:10.7150/jca.32608
Treatment of cancer cells with chemotherapeutic drugs results in profound changes in expression of genes encoding aldehyde-metabolizing enzymes
1. Engelhardt Institute of Molecular Biology, the Russian Academy of Sciences, 119991 Moscow, Russia
2. Institute of Biomedical Chemistry, the Russian Academy of Sciences, 119121 Moscow, Russia
Zinovieva OL, Grineva EN, Krasnov GS, Karpov DS, Zheltukhin AO, Snezhkina AV, Kudryavtseva AV, Mashkova TD, Lisitsyn NA. Treatment of cancer cells with chemotherapeutic drugs results in profound changes in expression of genes encoding aldehyde-metabolizing enzymes. J Cancer 2019; 10(18):4256-4263. doi:10.7150/jca.32608. Available from http://www.jcancer.org/v10p4256.htm
Using RNA-seq, RT-qPCR, and bioinformatics we have studied the influence of a wide spectrum of chemotherapeutic drugs on transcription of AKR1B10, AKR1C1, ALDH1A1, and ALDH1A3 genes, which encode the major aldehyde-metabolizing enzymes. The strongest alterations were detected in case of AKR1B10 mRNA that was significantly upregulated in wild type p53 cancer cells, but downregulated in mutant p53 cancer cells. Subsequent experiments demonstrated the significant and consistent decrease in the AKR1B10 mRNA content in sera of colon cancer patients, as compared to sera of healthy donors (p<0.0001, SPE=92.9%, SNE=79.3%, AUC=0.889), which implies that this RNA is a valuable marker for serological diagnosis of colorectal cancer. Moreover, we have found that ALDH1A3 protein is a key inactivator of ROS-generated aldehydes, which is a perspective target for the development of new chemotherapeutic drugs.
Keywords: colorectal cancer, chemotherapeutic drugs, reactive oxygen species, RNA-seq, serum biomarkers.