Department of Gastrointestinal Surgery, Hubei No. 3 People's Hospital of Jianghan University, Wuhan 430033, Hubei, China.
Department of Thyroid and Breast Surgery, Hubei No. 3 People's Hospital of Jianghan University, Wuhan 430033, Hubei, China.
Crit Rev Eukaryot Gene Expr. 2023;33(3):13-26. doi: 10.1615/CritRevEukaryotGeneExpr.2022043844.
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.
长链非编码 RNA（lncRNA）在甲状腺乳头状癌（PTC）中具有抑癌和致癌作用。在所有甲状腺癌中，PTC 最为常见。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。通过定量逆转录聚合酶链反应和 Western blot 实验确定 lncRNA XIST、miR-330-3p 和 PDE5A 的表达模式。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实验进一步证实。通过失活功能结合 Transwell、CCK-8 和 caspase-3 活性实验，确定 XIST/miR-330-3p/PDE5A 轴在调节 PTC 细胞恶性的机制。通过异种移植肿瘤实验研究 XIST 对体内肿瘤发展的影响。PTC 细胞系和组织表现出相当高的 lncRNA XIST 表达水平。XIST 敲低抑制 PTC 细胞增殖、阻断迁移并增强凋亡。此外，其敲低抑制了体内 PTC 肿瘤的发展。XIST 抑制 miR-330-3p 以刺激 PTC 的恶性行为。通过下调 PDE5A，miR-330-3p 减弱了 PTC 细胞生长、迁移和存活的能力。lncRNA XIST 通过调节 miR-330-3p/PDE5A 轴促进 PTC 肿瘤的发展。本研究的结果为 PTC 的治疗提供了新的思路。
