Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia
Drug resistance contributes to treatment failure and relapse in acute lymphoblastic leukemia (ALL). G1P3 (also known as IFI6, interferon, alpha-inducible protein 6) has been regarded as an antiapoptotic protein in myeloma cells and contributes to chemoresistance in breast cancer. However, the role o...
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De Gruyter
2022-02-01
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Online Access: | https://doi.org/10.1515/biol-2022-0011 |
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author | Zou Liping Liu Zhirui Li Xueer Liu Liping Zhu Ying |
author_facet | Zou Liping Liu Zhirui Li Xueer Liu Liping Zhu Ying |
author_sort | Zou Liping |
collection | DOAJ |
description | Drug resistance contributes to treatment failure and relapse in acute lymphoblastic leukemia (ALL). G1P3 (also known as IFI6, interferon, alpha-inducible protein 6) has been regarded as an antiapoptotic protein in myeloma cells and contributes to chemoresistance in breast cancer. However, the role of G1P3 in the proliferation and chemosensitivity of ALL is largely unknown. Data from colony formation and bromo-deoxyuridine (BrdU) incorporation assays showed that siRNA-mediated downregulation of G1P3 repressed cell proliferation of glucocorticoids-resistant human leukemic cells (CEM-C1), while overexpression of G1P3 promoted the cell proliferation. Cell apoptosis of CEM-C1 was suppressed by G1P3 overexpression accompanied by a decrease in cleaved caspase-3 and caspase-9. Knockdown of G1P3 increased protein expression of cleaved caspase-3 and caspase-9 to promote the cell apoptosis of CEM-C1. Moreover, silencing of G1P3 reduced cell viability and promoted cell apoptosis of CEM-C1 exposed to dexamethasone. The proapoptotic protein B-cell lymphoma 2 interacting mediator of cell death (Bim) was enhanced by the interference of G1P3 in CEM-C1. Silencing of Bim attenuated G1P3 interference-induced decrease in cell viability and increase in cell apoptosis in CEM-C1 exposed to dexamethasone. Conclusively, knockdown of G1P3 inhibited cell proliferation of ALL and sensitized glucocorticoid-resistant ALL cells to dexamethasone through upregulation of Bim-mediated cell apoptosis. |
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language | English |
last_indexed | 2024-04-12T03:01:14Z |
publishDate | 2022-02-01 |
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spelling | doaj.art-d969aab5148b46559bffdfa78e201fbb2022-12-22T03:50:40ZengDe GruyterOpen Life Sciences2391-54122022-02-01171647010.1515/biol-2022-0011Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemiaZou Liping0Liu Zhirui1Li Xueer2Liu Liping3Zhu Ying4Department of Blood Transfusion, First Affiliated Hospital of Gannan Medical University, Zhanggong District, Ganzhou, Jiangxi Province, 341000, ChinaHuman Aging Research Institute (HARI), Nanchang University, Nanchang, Jiangxi Province, 330031, ChinaHuman Aging Research Institute (HARI), Nanchang University, Nanchang, Jiangxi Province, 330031, ChinaDepartment of Hematology, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi Province, 341000, ChinaDepartment of Blood Transfusion, First Affiliated Hospital of Gannan Medical University, Zhanggong District, Ganzhou, Jiangxi Province, 341000, ChinaDrug resistance contributes to treatment failure and relapse in acute lymphoblastic leukemia (ALL). G1P3 (also known as IFI6, interferon, alpha-inducible protein 6) has been regarded as an antiapoptotic protein in myeloma cells and contributes to chemoresistance in breast cancer. However, the role of G1P3 in the proliferation and chemosensitivity of ALL is largely unknown. Data from colony formation and bromo-deoxyuridine (BrdU) incorporation assays showed that siRNA-mediated downregulation of G1P3 repressed cell proliferation of glucocorticoids-resistant human leukemic cells (CEM-C1), while overexpression of G1P3 promoted the cell proliferation. Cell apoptosis of CEM-C1 was suppressed by G1P3 overexpression accompanied by a decrease in cleaved caspase-3 and caspase-9. Knockdown of G1P3 increased protein expression of cleaved caspase-3 and caspase-9 to promote the cell apoptosis of CEM-C1. Moreover, silencing of G1P3 reduced cell viability and promoted cell apoptosis of CEM-C1 exposed to dexamethasone. The proapoptotic protein B-cell lymphoma 2 interacting mediator of cell death (Bim) was enhanced by the interference of G1P3 in CEM-C1. Silencing of Bim attenuated G1P3 interference-induced decrease in cell viability and increase in cell apoptosis in CEM-C1 exposed to dexamethasone. Conclusively, knockdown of G1P3 inhibited cell proliferation of ALL and sensitized glucocorticoid-resistant ALL cells to dexamethasone through upregulation of Bim-mediated cell apoptosis.https://doi.org/10.1515/biol-2022-0011g1p3allproliferationglucocorticoids-resistantdexamethasonebimapoptosis |
spellingShingle | Zou Liping Liu Zhirui Li Xueer Liu Liping Zhu Ying Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia Open Life Sciences g1p3 all proliferation glucocorticoids-resistant dexamethasone bim apoptosis |
title | Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia |
title_full | Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia |
title_fullStr | Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia |
title_full_unstemmed | Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia |
title_short | Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia |
title_sort | knockdown of g1p3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia |
topic | g1p3 all proliferation glucocorticoids-resistant dexamethasone bim apoptosis |
url | https://doi.org/10.1515/biol-2022-0011 |
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