Upregulation of Peroxiredoxin-2 in Well-Differentiated Pancreatic Neuroendocrine Tumors and Its Utility as a Biomarker for Predicting the Response to Everolimus
Pancreatic neuroendocrine neoplasms (pNENs) account for 2–3% of pancreatic malignancies. Peroxiredoxins (Prdxs), which are major cellular antioxidants, are involved in multiple oncogenic signaling pathways. We investigated the role of peroxiredoxin-2 in QGP-1 human pNEN cell line and patient-derived...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-11-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/9/11/1104 |
| _version_ | 1797548434470731776 |
|---|---|
| author | Eui Joo Kim Yoon Jae Kim Hye In Lee Seok-Hoo Jeong Hyo Jung Nam Jae Hee Cho |
| author_facet | Eui Joo Kim Yoon Jae Kim Hye In Lee Seok-Hoo Jeong Hyo Jung Nam Jae Hee Cho |
| author_sort | Eui Joo Kim |
| collection | DOAJ |
| description | Pancreatic neuroendocrine neoplasms (pNENs) account for 2–3% of pancreatic malignancies. Peroxiredoxins (Prdxs), which are major cellular antioxidants, are involved in multiple oncogenic signaling pathways. We investigated the role of peroxiredoxin-2 in QGP-1 human pNEN cell line and patient-derived pNEN tissue. To validate the cancer stem cell-like cell characteristics of QGP-1 cells in spheroid culture, in vitro analyses and xenografting were performed. Furthermore, immunohistochemical staining was conducted to verify the overexpression of Prdx2 in pNEN tissue. Prdx2 expression was high at the mRNA and protein levels in QGP-1 cells. Prdx2 was also overexpressed in patient-derived pNEN tissue. Silencing of Prdx2 using siRNA induced overexpression and phosphorylation of ERK and AKT in QGP-1. Cell proliferation was increased by treating QGP-1 cells with siPrdx2, and the IC50 of everolimus increased suggesting resistance to everolimus. Interestingly, QGP-1 spheroid cells, which exhibited cancer stem cell-like features, exhibited lower expression of Prdx2 and mTOR. The results suggest that Prdx2 expression level and its activity may be a potential predictive biomarker for therapeutic response or resistance to everolimus in pNEN. |
| first_indexed | 2024-03-10T14:59:19Z |
| format | Article |
| id | doaj.art-e5f2127cf55c4b9d9d460724f4b5987e |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T14:59:19Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-e5f2127cf55c4b9d9d460724f4b5987e2023-11-20T20:21:18ZengMDPI AGAntioxidants2076-39212020-11-01911110410.3390/antiox9111104Upregulation of Peroxiredoxin-2 in Well-Differentiated Pancreatic Neuroendocrine Tumors and Its Utility as a Biomarker for Predicting the Response to EverolimusEui Joo Kim0Yoon Jae Kim1Hye In Lee2Seok-Hoo Jeong3Hyo Jung Nam4Jae Hee Cho5Division of Gastroenterology, Department of Internal Medicine, Gil Medical Center, College of Medicine Gachon University, Incheon 21565, KoreaDivision of Gastroenterology, Department of Internal Medicine, Gil Medical Center, College of Medicine Gachon University, Incheon 21565, KoreaDivision of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, KoreaDivision of Gastroenterology, Department of Internal Medicine, Catholic Kwandong University International St. Mary’s Hospital, Incheon 22711, KoreaDivision of Gastroenterology, Department of Internal Medicine, Gil Medical Center, College of Medicine Gachon University, Incheon 21565, KoreaDivision of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, KoreaPancreatic neuroendocrine neoplasms (pNENs) account for 2–3% of pancreatic malignancies. Peroxiredoxins (Prdxs), which are major cellular antioxidants, are involved in multiple oncogenic signaling pathways. We investigated the role of peroxiredoxin-2 in QGP-1 human pNEN cell line and patient-derived pNEN tissue. To validate the cancer stem cell-like cell characteristics of QGP-1 cells in spheroid culture, in vitro analyses and xenografting were performed. Furthermore, immunohistochemical staining was conducted to verify the overexpression of Prdx2 in pNEN tissue. Prdx2 expression was high at the mRNA and protein levels in QGP-1 cells. Prdx2 was also overexpressed in patient-derived pNEN tissue. Silencing of Prdx2 using siRNA induced overexpression and phosphorylation of ERK and AKT in QGP-1. Cell proliferation was increased by treating QGP-1 cells with siPrdx2, and the IC50 of everolimus increased suggesting resistance to everolimus. Interestingly, QGP-1 spheroid cells, which exhibited cancer stem cell-like features, exhibited lower expression of Prdx2 and mTOR. The results suggest that Prdx2 expression level and its activity may be a potential predictive biomarker for therapeutic response or resistance to everolimus in pNEN.https://www.mdpi.com/2076-3921/9/11/1104pancreatic neuroendocrine neoplasmperoxiredoxinmTOR inhibitoreverolimus |
| spellingShingle | Eui Joo Kim Yoon Jae Kim Hye In Lee Seok-Hoo Jeong Hyo Jung Nam Jae Hee Cho Upregulation of Peroxiredoxin-2 in Well-Differentiated Pancreatic Neuroendocrine Tumors and Its Utility as a Biomarker for Predicting the Response to Everolimus Antioxidants pancreatic neuroendocrine neoplasm peroxiredoxin mTOR inhibitor everolimus |
| title | Upregulation of Peroxiredoxin-2 in Well-Differentiated Pancreatic Neuroendocrine Tumors and Its Utility as a Biomarker for Predicting the Response to Everolimus |
| title_full | Upregulation of Peroxiredoxin-2 in Well-Differentiated Pancreatic Neuroendocrine Tumors and Its Utility as a Biomarker for Predicting the Response to Everolimus |
| title_fullStr | Upregulation of Peroxiredoxin-2 in Well-Differentiated Pancreatic Neuroendocrine Tumors and Its Utility as a Biomarker for Predicting the Response to Everolimus |
| title_full_unstemmed | Upregulation of Peroxiredoxin-2 in Well-Differentiated Pancreatic Neuroendocrine Tumors and Its Utility as a Biomarker for Predicting the Response to Everolimus |
| title_short | Upregulation of Peroxiredoxin-2 in Well-Differentiated Pancreatic Neuroendocrine Tumors and Its Utility as a Biomarker for Predicting the Response to Everolimus |
| title_sort | upregulation of peroxiredoxin 2 in well differentiated pancreatic neuroendocrine tumors and its utility as a biomarker for predicting the response to everolimus |
| topic | pancreatic neuroendocrine neoplasm peroxiredoxin mTOR inhibitor everolimus |
| url | https://www.mdpi.com/2076-3921/9/11/1104 |
| work_keys_str_mv | AT euijookim upregulationofperoxiredoxin2inwelldifferentiatedpancreaticneuroendocrinetumorsanditsutilityasabiomarkerforpredictingtheresponsetoeverolimus AT yoonjaekim upregulationofperoxiredoxin2inwelldifferentiatedpancreaticneuroendocrinetumorsanditsutilityasabiomarkerforpredictingtheresponsetoeverolimus AT hyeinlee upregulationofperoxiredoxin2inwelldifferentiatedpancreaticneuroendocrinetumorsanditsutilityasabiomarkerforpredictingtheresponsetoeverolimus AT seokhoojeong upregulationofperoxiredoxin2inwelldifferentiatedpancreaticneuroendocrinetumorsanditsutilityasabiomarkerforpredictingtheresponsetoeverolimus AT hyojungnam upregulationofperoxiredoxin2inwelldifferentiatedpancreaticneuroendocrinetumorsanditsutilityasabiomarkerforpredictingtheresponsetoeverolimus AT jaeheecho upregulationofperoxiredoxin2inwelldifferentiatedpancreaticneuroendocrinetumorsanditsutilityasabiomarkerforpredictingtheresponsetoeverolimus |