Exosomal miR-543 Inhibits the Proliferation of Ovarian Cancer by Targeting IGF2
Objective. Ovarian cancer (OvCa) is the most lethal gynaecological malignancy worldwide. We aimed to illustrate the potential function and molecular mechanism of exosomal microRNA-543 (miR-543) in the oncogenesis and development of OvCa. Methods. Differentially expressed microRNAs in exosomes derive...
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Format: | Article |
Language: | English |
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Wiley
2022-01-01
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Series: | Journal of Immunology Research |
Online Access: | http://dx.doi.org/10.1155/2022/2003739 |
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author | Shupei Zhang Diling Pan Shaoyu Zhang Qiumei Wu Lan Zhen Shihuang Liu Jingjing Chen Rong Lin Qiuhua Hong Xiangqin Zheng Huan Yi |
author_facet | Shupei Zhang Diling Pan Shaoyu Zhang Qiumei Wu Lan Zhen Shihuang Liu Jingjing Chen Rong Lin Qiuhua Hong Xiangqin Zheng Huan Yi |
author_sort | Shupei Zhang |
collection | DOAJ |
description | Objective. Ovarian cancer (OvCa) is the most lethal gynaecological malignancy worldwide. We aimed to illustrate the potential function and molecular mechanism of exosomal microRNA-543 (miR-543) in the oncogenesis and development of OvCa. Methods. Differentially expressed microRNAs in exosomes derived from OvCa cell lines were identified by bioinformatic analysis and verified by RT-PCR. Cell proliferation ability was estimated by clonogenic and 5-ethynyl-2′-deoxyuridine assays in vitro and in vivo. Potential involved pathways and targets of exosomal miRNAs were analysed using DIANA and verified by pyrosequencing, glucose quantification, dual-luciferase reporter experiments, and functional rescue assays. Results. Bioinformatic analysis identified miR-543 and its potential target genes involved in the cancer-associated proteoglycan pathway. The expression of miR-543 was significantly decreased in exosomes derived from OvCa cell lines, patient serum, and OvCa tissues, while the mRNA levels of insulin-like growth factor 2 (IGF2) were increased. Furthermore, the overexpression of miR-543 resulted in the suppression of OvCa cell proliferation in vitro and in vivo. Moreover, miR-543 was significantly negatively correlated with IGF2 in OvCa tissues in comparison with paracarcinoma tissues. Notably, upregulation of miR-543 led to increased cell supernatant glucose levels and suppressed cell growth, which was rescued by overexpression of IGF2. Conclusions. Exosomal miR-543 participates in the proteoglycan pathway to suppress cell proliferation by targeting IGF2 in OvCa. |
format | Article |
id | doaj-art-0d5bdf6d76ed4785aea00edeabce26c4 |
institution | Kabale University |
issn | 2314-7156 |
language | English |
publishDate | 2022-01-01 |
publisher | Wiley |
record_format | Article |
series | Journal of Immunology Research |
spelling | doaj-art-0d5bdf6d76ed4785aea00edeabce26c42025-02-03T01:07:55ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/2003739Exosomal miR-543 Inhibits the Proliferation of Ovarian Cancer by Targeting IGF2Shupei Zhang0Diling Pan1Shaoyu Zhang2Qiumei Wu3Lan Zhen4Shihuang Liu5Jingjing Chen6Rong Lin7Qiuhua Hong8Xiangqin Zheng9Huan Yi10Gynaecology OncologyGynaecology OncologyObstetrics and GynaecologyGynaecology OncologyGynaecology OncologyGynaecology OncologyObstetrics and GynaecologyGynaecology OncologyGynaecology OncologyGynaecology OncologyGynaecology OncologyObjective. Ovarian cancer (OvCa) is the most lethal gynaecological malignancy worldwide. We aimed to illustrate the potential function and molecular mechanism of exosomal microRNA-543 (miR-543) in the oncogenesis and development of OvCa. Methods. Differentially expressed microRNAs in exosomes derived from OvCa cell lines were identified by bioinformatic analysis and verified by RT-PCR. Cell proliferation ability was estimated by clonogenic and 5-ethynyl-2′-deoxyuridine assays in vitro and in vivo. Potential involved pathways and targets of exosomal miRNAs were analysed using DIANA and verified by pyrosequencing, glucose quantification, dual-luciferase reporter experiments, and functional rescue assays. Results. Bioinformatic analysis identified miR-543 and its potential target genes involved in the cancer-associated proteoglycan pathway. The expression of miR-543 was significantly decreased in exosomes derived from OvCa cell lines, patient serum, and OvCa tissues, while the mRNA levels of insulin-like growth factor 2 (IGF2) were increased. Furthermore, the overexpression of miR-543 resulted in the suppression of OvCa cell proliferation in vitro and in vivo. Moreover, miR-543 was significantly negatively correlated with IGF2 in OvCa tissues in comparison with paracarcinoma tissues. Notably, upregulation of miR-543 led to increased cell supernatant glucose levels and suppressed cell growth, which was rescued by overexpression of IGF2. Conclusions. Exosomal miR-543 participates in the proteoglycan pathway to suppress cell proliferation by targeting IGF2 in OvCa.http://dx.doi.org/10.1155/2022/2003739 |
spellingShingle | Shupei Zhang Diling Pan Shaoyu Zhang Qiumei Wu Lan Zhen Shihuang Liu Jingjing Chen Rong Lin Qiuhua Hong Xiangqin Zheng Huan Yi Exosomal miR-543 Inhibits the Proliferation of Ovarian Cancer by Targeting IGF2 Journal of Immunology Research |
title | Exosomal miR-543 Inhibits the Proliferation of Ovarian Cancer by Targeting IGF2 |
title_full | Exosomal miR-543 Inhibits the Proliferation of Ovarian Cancer by Targeting IGF2 |
title_fullStr | Exosomal miR-543 Inhibits the Proliferation of Ovarian Cancer by Targeting IGF2 |
title_full_unstemmed | Exosomal miR-543 Inhibits the Proliferation of Ovarian Cancer by Targeting IGF2 |
title_short | Exosomal miR-543 Inhibits the Proliferation of Ovarian Cancer by Targeting IGF2 |
title_sort | exosomal mir 543 inhibits the proliferation of ovarian cancer by targeting igf2 |
url | http://dx.doi.org/10.1155/2022/2003739 |
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