CircRTN1作为miR-431-5p海绵,通过上调TGFA促进甲状腺癌进展。

Hormones (Athens, Greece) Pub Date : 2022-12-01 Epub Date: 2022-07-08 DOI:10.1007/s42000-022-00378-7
Yu Gao, Yichun Wang, Lei Xu, Xiaoque Xie, Liyang Zhu, Fan Wang
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引用次数: 1

摘要

目的:本研究旨在探讨环状RNA (circRNA)网状1 (circRTN1)在甲状腺癌(TC)中的作用及其机制。方法:采用实时荧光定量PCR (qRT-PCR)检测circRTN1、microRNA-431-5p (miR-431-5p)、转化生长因子- α (TGFA) mRNA的表达水平。利用集落形成和5-乙基-2'-脱氧尿苷(EdU)测定来评估细胞增殖。流式细胞术分析细胞凋亡。采用transwell法测定细胞迁移和侵袭。Western blot法检测ki-67、Bax、基质金属蛋白酶2 (MMP-2)、TGFA蛋白水平。通过双荧光素酶报告基因法和RNA免疫沉淀(RIP)法验证miR-431-5p与circRTN1或TGFA之间的相互作用。通过异种移植肿瘤实验探讨circrtn1对体内TC的影响。结果:circRTN1在TC组织和细胞中表达升高。敲低circRTN1抑制TC细胞增殖、迁移和侵袭,增加细胞凋亡。MiR-431-5p是circRTN1的靶标,MiR-431-5p下调逆转了TC细胞中circRTN1敲低的作用。TGFA被确定为miR-431-5p的直接靶点,miR-431-5p通过下调TGFA在TC细胞中发挥抗肿瘤作用。此外,circRTN1海绵miR-431-5p调节TGFA的表达。此外,circRTN1敲低可抑制体内肿瘤生长。结论:CircRTN1通过调节miR-431-5p/TGFA轴在TC中作为促癌circRNA,为TC治疗提供了潜在的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CircRTN1 acts as a miR-431-5p sponge to promote thyroid cancer progression by upregulating TGFA.

Purpose: This study aimed to explore the role and underlying mechanism of circular RNA (circRNA) reticulon 1 (circRTN1) in thyroid cancer (TC).

Methods: The expression levels of circRTN1, microRNA-431-5p (miR-431-5p), and transforming growth factor-alpha (TGFA) mRNA were measured by quantitative real-time PCR (qRT-PCR). Cell proliferation was evaluated using colony formation and 5-ethynyl-2'-deoxyuridine (EdU) assays. Cell apoptosis was analyzed using flow cytometry. Cell migration and invasion were measured using the transwell assay. The protein levels of ki-67, Bax, matrix metalloproteinase 2 (MMP-2), and TGFA were detected using Western blot assay. The interaction between miR-431-5p and circRTN1 or TGFA was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The effect of circRTN1on TC in vivo was explored via xenograft tumor assay.

Results: The expression of circRTN1 was increased in TC tissues and cells. Knockdown of circRTN1 suppressed TC cell proliferation, migration, and invasion, and increased cell apoptosis. MiR-431-5p was a target of circRTN1, and miR-431-5p downregulation reversed the role of circRTN1 knockdown in TC cells. TGFA was identified as a direct target of miR-431-5p, and miR-431-5p exerted the anti-tumor role in TC cells by downregulating TGFA. Moreover, circRTN1 sponged miR-431-5p to regulate TGFA expression. Furthermore, circRTN1 knockdown inhibited tumor growth in vivo.

Conclusion: CircRTN1 acted as a cancer-promoting circRNA in TC by regulating the miR-431-5p/TGFA axis, providing a potential therapeutic strategy for TC treatment.

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