Identification of New Regulators of Pancreatic Cancer Cell Sensitivity to Oxaliplatin and Cisplatin
The chemoresistance of tumor cells is one of the most urgent challenges in modern oncology and in pancreatic cancer, in which this problem is the most prominent. Therefore, the identification of new chemosensitizing co-targets may be a path toward increasing chemotherapy efficacy. In this work, we p...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-02-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/4/1289 |
| _version_ | 1797477654212902912 |
|---|---|
| author | Vera Skripova Ramilia Vlasenkova Yan Zhou Igor Astsaturov Ramziya Kiyamova |
| author_facet | Vera Skripova Ramilia Vlasenkova Yan Zhou Igor Astsaturov Ramziya Kiyamova |
| author_sort | Vera Skripova |
| collection | DOAJ |
| description | The chemoresistance of tumor cells is one of the most urgent challenges in modern oncology and in pancreatic cancer, in which this problem is the most prominent. Therefore, the identification of new chemosensitizing co-targets may be a path toward increasing chemotherapy efficacy. In this work, we performed high-performance in vitro knockout CRISPR/Cas9 screening to find potential regulators of the sensitivity of pancreatic cancer. For this purpose, MIA PaCa-2 cells transduced with two sgRNA libraries (“cell cycle/nuclear proteins genes” and “genome-wide”) were screened by oxaliplatin and cisplatin. In total, 173 candidate genes were identified as potential regulators of pancreatic cancer cell sensitivity to oxaliplatin and/or cisplatin; among these, 25 genes have previously been reported, while 148 genes were identified for the first time as potential platinum drug sensitivity regulators. We found seven candidate genes involved in pancreatic cancer cell sensitivity to both cisplatin and oxaliplatin. Gene ontology enrichment analysis reveals the enrichment of single-stranded DNA binding, damaged DNA binding pathways, and four associated with NADH dehydrogenase activity. Further investigation and validation of the obtained results by in vitro, in vivo, and bioinformatics approaches, as well as literature analysis, will help to identify novel pancreatic cancer platinum sensitivity regulators. |
| first_indexed | 2024-03-09T21:20:49Z |
| format | Article |
| id | doaj.art-68eed9bd192b4ee4b07412e95cbec42a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T21:20:49Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-68eed9bd192b4ee4b07412e95cbec42a2023-11-23T21:21:41ZengMDPI AGMolecules1420-30492022-02-01274128910.3390/molecules27041289Identification of New Regulators of Pancreatic Cancer Cell Sensitivity to Oxaliplatin and CisplatinVera Skripova0Ramilia Vlasenkova1Yan Zhou2Igor Astsaturov3Ramziya Kiyamova4“Biomarker” Research Laboratory, Institute of Fundamental Biology and Medicine, Kazan Federal University, 420008 Kazan, Russia“Biomarker” Research Laboratory, Institute of Fundamental Biology and Medicine, Kazan Federal University, 420008 Kazan, RussiaInstitute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USAInstitute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA“Biomarker” Research Laboratory, Institute of Fundamental Biology and Medicine, Kazan Federal University, 420008 Kazan, RussiaThe chemoresistance of tumor cells is one of the most urgent challenges in modern oncology and in pancreatic cancer, in which this problem is the most prominent. Therefore, the identification of new chemosensitizing co-targets may be a path toward increasing chemotherapy efficacy. In this work, we performed high-performance in vitro knockout CRISPR/Cas9 screening to find potential regulators of the sensitivity of pancreatic cancer. For this purpose, MIA PaCa-2 cells transduced with two sgRNA libraries (“cell cycle/nuclear proteins genes” and “genome-wide”) were screened by oxaliplatin and cisplatin. In total, 173 candidate genes were identified as potential regulators of pancreatic cancer cell sensitivity to oxaliplatin and/or cisplatin; among these, 25 genes have previously been reported, while 148 genes were identified for the first time as potential platinum drug sensitivity regulators. We found seven candidate genes involved in pancreatic cancer cell sensitivity to both cisplatin and oxaliplatin. Gene ontology enrichment analysis reveals the enrichment of single-stranded DNA binding, damaged DNA binding pathways, and four associated with NADH dehydrogenase activity. Further investigation and validation of the obtained results by in vitro, in vivo, and bioinformatics approaches, as well as literature analysis, will help to identify novel pancreatic cancer platinum sensitivity regulators.https://www.mdpi.com/1420-3049/27/4/1289pancreatic cancerchemotherapy resistanceoxaliplatincisplatinCRISPR/Cas9 screeningbiomarkers |
| spellingShingle | Vera Skripova Ramilia Vlasenkova Yan Zhou Igor Astsaturov Ramziya Kiyamova Identification of New Regulators of Pancreatic Cancer Cell Sensitivity to Oxaliplatin and Cisplatin Molecules pancreatic cancer chemotherapy resistance oxaliplatin cisplatin CRISPR/Cas9 screening biomarkers |
| title | Identification of New Regulators of Pancreatic Cancer Cell Sensitivity to Oxaliplatin and Cisplatin |
| title_full | Identification of New Regulators of Pancreatic Cancer Cell Sensitivity to Oxaliplatin and Cisplatin |
| title_fullStr | Identification of New Regulators of Pancreatic Cancer Cell Sensitivity to Oxaliplatin and Cisplatin |
| title_full_unstemmed | Identification of New Regulators of Pancreatic Cancer Cell Sensitivity to Oxaliplatin and Cisplatin |
| title_short | Identification of New Regulators of Pancreatic Cancer Cell Sensitivity to Oxaliplatin and Cisplatin |
| title_sort | identification of new regulators of pancreatic cancer cell sensitivity to oxaliplatin and cisplatin |
| topic | pancreatic cancer chemotherapy resistance oxaliplatin cisplatin CRISPR/Cas9 screening biomarkers |
| url | https://www.mdpi.com/1420-3049/27/4/1289 |
| work_keys_str_mv | AT veraskripova identificationofnewregulatorsofpancreaticcancercellsensitivitytooxaliplatinandcisplatin AT ramiliavlasenkova identificationofnewregulatorsofpancreaticcancercellsensitivitytooxaliplatinandcisplatin AT yanzhou identificationofnewregulatorsofpancreaticcancercellsensitivitytooxaliplatinandcisplatin AT igorastsaturov identificationofnewregulatorsofpancreaticcancercellsensitivitytooxaliplatinandcisplatin AT ramziyakiyamova identificationofnewregulatorsofpancreaticcancercellsensitivitytooxaliplatinandcisplatin |