Table 4.
A list showing several genes which have been reported as being implicated in gemcitabine resistance.
| Gene ID | log2FC for GemMIA-R3 vs parental | log2FC for CM03 in parental cells | log2FC for CM03 in GemMIA-R3 cells | No. of PQs | Role in gemcitabine resistance | Refs. |
|---|---|---|---|---|---|---|
| dCK | − 2.99 | − 0.37 | − 0.30 | 2 | The deoxycytidine kinase (dCK) enzyme metabolizes and activates gemcitabine | 13 |
| CDA | 5.08 | 0.52 | 0.44 | 4 | High level of cytidine deaminase (CDA) enzyme metabolizes gemcitabine leading to resistance | 16 |
| RRM1 | 0.70 | − 0.38 | − 0.09 | 7 | The overexpression of ribonucleoside-diphosphate reductase M1 and M2 (RRM1/2) genes reduce gemcitabine metabolism, leading to resistance | 18 |
| RRM2 | 0.34 | − 0.48 | − 0.50 | 3 | ||
| SHH | 3.50 | 0.86 | − 0.16 | 17 | Deregulated hedgehog pathway is associated with gem-resistance where SHH ligand is overexpressed | 14 |
| GLI1 | 3.60 | − 0.64 | − 0.57 | 15 | GLI transcription factors promote gem-resistance via SOX2 overexpression | 23 |
| ABCC4 | 0.77 | 0.02 | − 0.05 | 28 | Overexpressed multidrug resistance gene, increases drug efflex | 15 |
| MAPK11 | 0.00 | − 2.56 | − 3.03 | 18 | MAPK signalling pathway | 19 |
| MAPK12 | 0.05 | − 1.23 | − 1.83 | 18 | 19 | |
| AKT1 | 0.10 | − 0.98 | − 1.55 | 44 | AKT signalling pathway | 14 |
| FOXM1 | − 0.16 | − 0.13 | − 0.52 | 2 | Oncogenic transcription factor which is associated with gem-resistance | 14 |
| ST6GAL1 | 2.84 | − 0.11 | − 1.16 | 21 | Promotes gem-resistance by abolishing gem-mediated DNA damage | 21 |
| FASN | 0.31 | − 0.54 | − 1.17 | 40 | Increase in fatty acid synthase (FASN) expression correlates with increased gem-resistance | 20 |
The effects of CM03 on their expression in the parental and resistant GemMIA-R3 cells (following 24 h exposure to CM03) are shown. There are many changes in expression for genes associated with gemcitabine resistance. There is also a trend for the genes previously identified with CM03-induced down-regulation in the parental cells (highlighted in bold), to be more down-regulated in the GemMIA-R3 line. The number of putative quadruplexes (PQs) in each gene were taken from the earlier study27, computed as reported previously52,53 and using the occurrence of the canonical G4 motif (G≥3N1−7G≥3N1−7G≥3N1−7G≥3).