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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Main Authors: Shupei Zhang, Diling Pan, Shaoyu Zhang, Qiumei Wu, Lan Zhen, Shihuang Liu, Jingjing Chen, Rong Lin, Qiuhua Hong, Xiangqin Zheng, Huan Yi
Format: Article
Language:English
Published: Wiley 2022-01-01
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.
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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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