Differential Expression of Cancer-Related miRNAs in Response to Chemotherapeutics and the Regulatory Axis of miR-595/E2F7 in Colorectal Cancer Cells
Abstract
MicroRNAs (miRNAs) are critical post-transcriptional regulators of gene expression and play key roles in cancer progression and chemoresistance. In this study, we investigated the expression profiles of selected cancer-associated miRNAs in response to two chemotherapeutic agents, docetaxel and lapatinib, in colorectal cancer cell lines. We also explored the potential regulatory interaction between miR-595 and the oncogene E2F7. Colorectal cancer cells (HT-29 and HCT-116) were treated with the IC₅₀ concentrations of docetaxel and lapatinib. RT-qPCR analysis revealed that docetaxel treatment significantly upregulated miR-718, miR-206, miR-1199, and miR-595 in HT-29 cells. In contrast, only miR-206 was upregulated, while the other genes were downregulated in HCT-116 cells. Lapatinib moderately increased the expression of the selected miRNAs in HT-29 cells but consistently downregulated all four miRNAs in HCT-116 cells. Bioinformatic analysis using TargetScan identified E2F7 as a potential target of miR-595. E2F7 expression was found to be elevated in colorectal cancer and further increased in docetaxel-treated HT-29 cells, suggesting a role in drug resistance. Overexpression of miR-595 resulted in the downregulation of E2F7, supporting a regulatory interaction. These findings suggest that miR-595 negatively regulates E2F7 and may contribute to modulating chemoresistance in colorectal cancer. Targeting the miR-595/E2F7 axis may offer a novel therapeutic strategy to enhance the efficacy of chemotherapy in colorectal cancer treatment.
Keywords
miRNAs, E2F7, chemoresistance, colorectal cancer
Ethical Statement
This study did not require ethical approval.
References
- F. Bray, J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, A. Jemal, Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA: Cancer Journal Clinicians 68 (6) (2018) 394–424.
- E. Cacan, Z. C. Ozmen, Regulation of Fas in response to bortezomib and epirubicin in colorectal cancer cells, J Chemother 32 (4) (2020) 193–201.
- B. Kucuk, E. Yilmaz, E. Cacan, Expression profiles of Natural Killer Group 2D Ligands (NGK2DLs) in colorectal carcinoma and changes in response to chemotherapeutic agents, Molecular Biology Reports 48 (5) (2021) 3999–4008.
- E. R. Fearon, B. Vogelstein, A genetic model for colorectal tumorigenesis, Cell 61 (5) (1990) 759–767.
- C. Berkel, E. Cacan, Transcriptomic analysis reveals tumor stage- or grade-dependent expression of miRNAs in serous ovarian cancer, Human Cell 34 (3) (2021) 862–877.
- Z. A. Syeda, S. S. S. Langden, C. Munkhzul, M. Lee, S. J. Song, Regulatory mechanism of microRNA expression in cancer, International Journal of Molecular Sciences 21 (5) (2020) 1723.
- M. Hill, N. Tran, miRNA interplay: mechanisms and consequences in cancer, Disease Models&Mechanisms 14 (4) (2021) dmm047662.
- R. Garzon, G. A. Calin, C. M. Croce, MicroRNAs in cancer, Annual Revıew of Medıcıne 60 (2009) 167–179.
- N. Valeri, P. Gasparini, C. Braconi, A. Paone, F. Lovat, M. Fabbri, K. M. Sumani, H. Alder, D. Amadori, T. Patel, G. J. Nuovo, R. Fishel, C. M. Croce, MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2), Proceedings of the National Academy of Sciences USA 107 (49) (2010) 21098–21103.
- H. Siemens, R. Jackstadt, S. Hünten, M. Kaller, A. Menssen, U. Götz, H. Hermeking, miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions, Cell Cycle 10 (24) (2011) 4256–4271.