Transcriptomic Profiling Reveals AKR1C1 and AKR1C3 Mediate Cisplatin Resistance in Signet Ring Cell Gastric Carcinoma via Autophagic Cell Death
Abstract
:1. Introduction
2. Results
2.1. Long-Term Exposure to Cisplatin Treatment Can Promote Drug Resistance in SRCGC
2.2. Identification of Candidate Genes to Promote Cisplatin Resistance in SRCGC Using Transcriptomic Sequencing
2.3. Verification of Cisplatin Resistance Related Genes in KATO/DDP Cell Line
2.4. Inhibition of AKR1C1 and AKR1C3 in Resensitizing the Cisplatin Cytotoxicity
2.5. Inhibition of AKR1C1- and AKR1C3-Induced Cell Death via Autophagy
2.6. AKR1C1 and 1C3 Mediated Chemo-Resistance in KATO/DPP by Regulating Redox Homeostasis
3. Discussion
4. Materials and Methods
4.1. Chemicals and Reagents
4.2. Cell Line and Culture Condition
4.3. Establishment of Cisplatin Resistance Gastric Cancer Cell Line
4.4. Cell Viability Test
4.5. RNA Isolation, Transcriptomic Sequencing, and Analysis
4.6. RNA Isolation, Reverse Transcription, and Quantitative PCR
4.7. Western Blotting Analysis
4.8. Intracellular ROS Measurement
4.9. Apoptosis Assay
4.10. Monodensylcadaverine Staining
4.11. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
3-MA | 3-Methyladenine |
5PBSA | 3-Bromo-5-phenylsalicylic acid |
AKR | Aldoketoreductase |
AKR1C1 | Aldoketoreductase1C1 |
AKR1C3 | Aldoketoreductase1C3 |
CYPs | Microsomal cytochrome P450 enzymes |
DCF-DA | 2’,7’-Dichlorofluorescin diacetate |
DEGs | Diffrentially expressed genes |
DMEM | Dulbecco’s Modified Eagle Medium |
FBS | Fetal bovine serum |
GO | Gene ontology |
HNE | 4-Hydroxynonenal |
MDC | Monodansylcadaverine |
NAC | N acetyl cysteine |
NCBI | National center for biotechnology information |
Nrf2 | Nuclear factor erythroid related factor 2 |
PBS | Phosphate-buffered saline |
QC | Quality Control |
ROS | Reactive oxygen species |
SRA | Sequence read archive |
SRCGC | Signet ring cell gastric carcinoma |
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Phoo, N.L.L.; Dejkriengkraikul, P.; Khaw-On, P.; Yodkeeree, S. Transcriptomic Profiling Reveals AKR1C1 and AKR1C3 Mediate Cisplatin Resistance in Signet Ring Cell Gastric Carcinoma via Autophagic Cell Death. Int. J. Mol. Sci. 2021, 22, 12512. https://doi.org/10.3390/ijms222212512
Phoo NLL, Dejkriengkraikul P, Khaw-On P, Yodkeeree S. Transcriptomic Profiling Reveals AKR1C1 and AKR1C3 Mediate Cisplatin Resistance in Signet Ring Cell Gastric Carcinoma via Autophagic Cell Death. International Journal of Molecular Sciences. 2021; 22(22):12512. https://doi.org/10.3390/ijms222212512
Chicago/Turabian StylePhoo, Nang Lae Lae, Pornngarm Dejkriengkraikul, Patompong Khaw-On, and Supachai Yodkeeree. 2021. "Transcriptomic Profiling Reveals AKR1C1 and AKR1C3 Mediate Cisplatin Resistance in Signet Ring Cell Gastric Carcinoma via Autophagic Cell Death" International Journal of Molecular Sciences 22, no. 22: 12512. https://doi.org/10.3390/ijms222212512