Exosomal miR-543 Inhibits the Proliferation of Ovarian Cancer by Targeting IGF2. (29th March 2022)

• Record Type: Journal Article
• Authors: Zhang, Shupei; Pan, Diling; Zhang, Shaoyu; Wu, Qiumei; Zhen, Lan; Liu, Shihuang; Chen, Jingjing; Lin, Rong; Hong, Qiuhua; Zheng, Xiangqin; Yi, Huan
• Other Names: Wang Xu Academic Editor.
• Is Part Of: Journal of immunology research. Volume 2022(2022)
• Publication Date: 2022-03-29
• Subjects: Immunology -- Periodicals; Immunology -- Research -- Periodicals; 616.07905
• DOI: 10.1155/2022/2003739
• Languages: English
• ISSNs: 2314-8861

Abstract

Abstract : 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.