Zinc oxide nanoparticle attenuates chemotherapy resistance by inducing cell stemness progression of colorectal cancer via miR-1321/HIF-2α axis

Background: Colorectal cancer (CRC) is the most malignant cancer type with high morbidity and mortality worldwide. Developed drug resistance severely affected the prognosis of CRC patients. This work aimed to explore the effects of zinc oxide nanoparticles (ZONs) in chemo-resistant CRC. Methods: We...

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Main Authors: Hua Ye, Kefeng Wu, Yi Liu, Yuzhen Zhu, Hui Luo, Wenying Zou
Format: Article
Language:English
Published: Elsevier 2022-07-01
Series:Arabian Journal of Chemistry
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1878535222002544
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author Hua Ye
Kefeng Wu
Yi Liu
Yuzhen Zhu
Hui Luo
Wenying Zou
author_facet Hua Ye
Kefeng Wu
Yi Liu
Yuzhen Zhu
Hui Luo
Wenying Zou
author_sort Hua Ye
collection DOAJ
description Background: Colorectal cancer (CRC) is the most malignant cancer type with high morbidity and mortality worldwide. Developed drug resistance severely affected the prognosis of CRC patients. This work aimed to explore the effects of zinc oxide nanoparticles (ZONs) in chemo-resistant CRC. Methods: We established Oxaliplatin (Oxa)-resistant CRC cells, and in vitro and in vivo model to evaluate the function effect of ZONs. Cell counting kit-8 (CCK-8), colony formation, and 5-ethynyl-2′-deoxyuridine (EDU) assay were performed to detect CRC cell viability and proliferation. CRC cell apoptosis was checked by flow cytometry. Tumor cell proliferation was checked by immunohistochemistry (IHC). Cell stemness was determined by sphere formation assay. Luciferase reporter gene assay was conducted to assess the binding of miR-1321 and HIF-2α 3′UTR region. Results: ZONs suppressed the viability and proliferation of Oxa-resistant CRC cells both in vitro and in vivo. ZONs suppressed CRC cell stemness and enhanced the sensitivity of CRC cells to chemo-therapy, along with decreased expression of stem cell biomarkers. ZONs elevated level of miR-1321 and reduced level of HIF-2α in CRC cells. MiR-1321 targeted the 3′UTR region of HIF-2α to suppress its expression. ZONs repressed HIF-2α expression by inducing miR-1321 in CRC cells. Conclusion: ZONs treatment remarkably converted the drug resistance and stemness of CRC cells, via upregulating miR-1321 to repress the expression of HIF-2α. Our findings suggested that ZONs are potential and effective agent for chemo-resistant CRC patients.
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spelling doaj.art-5e3cc765b14d45f68847373f8fe28b802022-12-22T00:26:21ZengElsevierArabian Journal of Chemistry1878-53522022-07-01157103938Zinc oxide nanoparticle attenuates chemotherapy resistance by inducing cell stemness progression of colorectal cancer via miR-1321/HIF-2α axisHua Ye0Kefeng Wu1Yi Liu2Yuzhen Zhu3Hui Luo4Wenying Zou5The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China; The Marine Biomedical Research Institute of Guangdon Zhanjiang, Zhanjiang 524023, Guangdong Province, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524023, Guangdong Province, China; Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China; Corresponding authors at: The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China (H. Ye, WY. Zou).The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524023, Guangdong Province, ChinaSouthern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524023, Guangdong Province, ChinaThe Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524023, Guangdong Province, China; Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, ChinaThe Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China; The Marine Biomedical Research Institute of Guangdon Zhanjiang, Zhanjiang 524023, Guangdong Province, China; Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, ChinaThe Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China; The Marine Biomedical Research Institute of Guangdon Zhanjiang, Zhanjiang 524023, Guangdong Province, China; Corresponding authors at: The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China (H. Ye, WY. Zou).Background: Colorectal cancer (CRC) is the most malignant cancer type with high morbidity and mortality worldwide. Developed drug resistance severely affected the prognosis of CRC patients. This work aimed to explore the effects of zinc oxide nanoparticles (ZONs) in chemo-resistant CRC. Methods: We established Oxaliplatin (Oxa)-resistant CRC cells, and in vitro and in vivo model to evaluate the function effect of ZONs. Cell counting kit-8 (CCK-8), colony formation, and 5-ethynyl-2′-deoxyuridine (EDU) assay were performed to detect CRC cell viability and proliferation. CRC cell apoptosis was checked by flow cytometry. Tumor cell proliferation was checked by immunohistochemistry (IHC). Cell stemness was determined by sphere formation assay. Luciferase reporter gene assay was conducted to assess the binding of miR-1321 and HIF-2α 3′UTR region. Results: ZONs suppressed the viability and proliferation of Oxa-resistant CRC cells both in vitro and in vivo. ZONs suppressed CRC cell stemness and enhanced the sensitivity of CRC cells to chemo-therapy, along with decreased expression of stem cell biomarkers. ZONs elevated level of miR-1321 and reduced level of HIF-2α in CRC cells. MiR-1321 targeted the 3′UTR region of HIF-2α to suppress its expression. ZONs repressed HIF-2α expression by inducing miR-1321 in CRC cells. Conclusion: ZONs treatment remarkably converted the drug resistance and stemness of CRC cells, via upregulating miR-1321 to repress the expression of HIF-2α. Our findings suggested that ZONs are potential and effective agent for chemo-resistant CRC patients.http://www.sciencedirect.com/science/article/pii/S1878535222002544Colorectal cancerZinc oxide nanoparticlesStemnessmiR-1321HIF-2α
spellingShingle Hua Ye
Kefeng Wu
Yi Liu
Yuzhen Zhu
Hui Luo
Wenying Zou
Zinc oxide nanoparticle attenuates chemotherapy resistance by inducing cell stemness progression of colorectal cancer via miR-1321/HIF-2α axis
Arabian Journal of Chemistry
Colorectal cancer
Zinc oxide nanoparticles
Stemness
miR-1321
HIF-2α
title Zinc oxide nanoparticle attenuates chemotherapy resistance by inducing cell stemness progression of colorectal cancer via miR-1321/HIF-2α axis
title_full Zinc oxide nanoparticle attenuates chemotherapy resistance by inducing cell stemness progression of colorectal cancer via miR-1321/HIF-2α axis
title_fullStr Zinc oxide nanoparticle attenuates chemotherapy resistance by inducing cell stemness progression of colorectal cancer via miR-1321/HIF-2α axis
title_full_unstemmed Zinc oxide nanoparticle attenuates chemotherapy resistance by inducing cell stemness progression of colorectal cancer via miR-1321/HIF-2α axis
title_short Zinc oxide nanoparticle attenuates chemotherapy resistance by inducing cell stemness progression of colorectal cancer via miR-1321/HIF-2α axis
title_sort zinc oxide nanoparticle attenuates chemotherapy resistance by inducing cell stemness progression of colorectal cancer via mir 1321 hif 2α axis
topic Colorectal cancer
Zinc oxide nanoparticles
Stemness
miR-1321
HIF-2α
url http://www.sciencedirect.com/science/article/pii/S1878535222002544
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