MiR-29a-5p inhibits proliferation and invasion and induces apoptosis in endometrial carcinoma via targeting TPX2. Issue 10 (19th May 2018)

• Record Type: Journal Article
• Authors: Jiang, Tiechao; Sui, Dongming; You, Dong; Yao, Songmei; Zhang, Lirong; Wang, Yingjian; Zhao, Jixue; Zhang, Yaozhong
• Is Part Of: Cell cycle. Volume 17:Issue 10(2018)
• Page Start: 1268
• Page End: 1278
• Publication Date: 2018-05-19
• Subjects: Endometrial carcinoma -- MiR-29a-5p -- TPX2; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2018.1475829
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: This study was aimed to explore the effects of miR-29a-5p expression and its target gene TPX2 (target protein for Xenopus kinesin-like protein 2) on endometrial cancer (EC) devel on EC development and to assess the prognostic impacts of TPX2. Microarray-based GEO and TCGA (the Cancer Genome Atlas) EC expression data were used to identify differentially expressed miRNAs and mRNAs. The observed potential target relationship between miR-29a-5p and TPX2 was verified using TargetScan and luciferase reporter assays. The mRNA and protein expression levels of miR-29a-5p and TPX2 were confirmed by qRT-PCR and western blot, respectively. Associations between TPX2 expression and patient prognosis were assessed using Kaplan-Meier and log-rank assays. Changes in EC-derived cell proliferation, invasion and apoptosis after exogenous miR-29a-5p and TPX2 over-expression and/or silencing were assessed using CCK-8 (cell counting kit-8), colony formation, Transwell and flow cytometry assays, respectively. We found that in primary EC tissues the expression of miR-29a-5p was down-regulated and the expression of TPX2 was up-regulated. We also found that low expression of TPX2 were associated with a better prognosis, and vice versa . Subsequent exogenous miR-29a-5p over-expression and TPX2 silencing could inhibit EC-derived cell proliferation and invasion, and to induce apoptosis. We also found that miR-29a-5p might target and repress TPX2, thereby inhibiting EC-derived cell proliferation and invasion and enhancing apoptosis. We conclude that miR-29a-5p could inhibit the proliferation and invasion of EC-derived cells and enhance the apoptosis of EC-derived cells via TPX2 down-regulation. A high TPX2 expression in primary EC tissues was found to be associated with a poor prognosis. As such, these biomarkers may serve as promising prognostic indicators. ABBREVIATIONS: EC: Endometrial cancer; 3ʹ-UTR: 3ʹ-untranslated regions; TPX2: target protein for Xenopus kinesin-like protein 2; TCGA: the Cancer Genome Atlas; UCEC: uterine corpus endometrial carcinoma; CCK-8: cell counting kit-8; OD: optical density; FCM: flow cytometry; EMT: epithelial-mesenchymal transition