IncRNA XIST通过miR-330-3p/PDE5A轴刺激甲状腺乳头状癌的发展。

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Tao Cai, Yan He, Binyu Peng
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引用次数: 1

摘要

长链非编码rna (lncRNAs)在甲状腺乳头状癌(PTC)中具有抑瘤和致癌功能。在所有甲状腺癌中,PTC是最常见的形式。在此,我们旨在确定lncRNA XIST在PTC增殖、侵袭和存活中的调控机制和功能。采用定量逆转录聚合酶链反应和Western blot实验检测lncRNA XIST、miR-330-3p和PDE5A的表达规律。通过亚细胞分离确定XIST的亚细胞定位。通过生物信息学分析确定miR-330-3p与XIST和PDE5A的关系,并通过荧光素酶报告基因检测进一步证实。通过功能缺失联合Transwell、CCK-8和caspase-3活性实验,确定XIST/miR-330-3p/PDE5A轴调控PTC细胞恶性肿瘤的机制。采用异种移植肿瘤实验研究XIST对体内肿瘤发展的影响。PTC细胞系和组织中lncRNA XIST的表达水平相当高。XIST基因敲低可抑制PTC细胞增殖、阻断迁移、增强细胞凋亡。此外,它的敲除抑制了PTC肿瘤在体内的发展。XIST通过抑制miR-330-3p刺激PTC的恶性行为。miR-330-3p通过下调PDE5A,减弱PTC细胞的生长、迁移和存活能力。lncRNA XIST通过调控miR-330-3p/PDE5A轴促进PTC的肿瘤发展。本研究结果为PTC的治疗提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
IncRNA XIST Stimulates Papillary Thyroid Cancer Development through the miR-330-3p/PDE5A Axis.

Long non-coding RNAs (lncRNAs) possess both tumor suppressive and oncogenic functions in papillary thyroid cancer (PTC). Among all the thyroid cancers, PTC is the most prevalent form. Herein, we aim to determine the regulatory mechanisms and functions of lncRNA XIST in the multiplication, invasion, and survival of PTC. Quantitative reverse transcription polymerase chain reaction and Western blot experiments were performed to determine the patterns of lncRNA XIST, miR-330-3p, and PDE5A expressions. The subcellular localization of XIST was determined through subcellular fractionation. Bioinformatics analyses were performed to determine miR-330-3p's relationships with XIST and PDE5A, which were further confirmed through luciferase reporter assays. Loss-of-function combined with Transwell, CCK-8, and caspase-3 activity experiments were performed to determine the mechanism of the XIST/miR-330-3p/PDE5A axis in regulating the malignancy of PTC cells. Xenograft tumor experiment was employed to study the influence of XIST on tumor development in vivo. The PTC cell lines and tissues manifested considerably high levels of lncRNA XIST expression. The XIST knockdown inhibited proliferation, blocked migration, and strengthened apoptosis among PTC cells. Moreover, its knockdown suppressed PTC tumor development in vivo. XIST repressed miR-330-3p to stimulate the malignant behaviors of PTC. Through the downregulation of PDE5A, miR-330-3p attenuated the capability of PTC cells to grow, migrate, and survive. lncRNA XIST promotes tumor development in PTC through the regulation of the miR-330-3p/PDE5A axis. The findings from this study provide new insights into the treatment of PTC.

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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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