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环状 RNA ITCH 通过 miR-106a-5p/JAZF1 轴抑制甲状腺乳头状癌中的上皮-间充质转化并促进细胞凋亡。

CircRNA ITCH Inhibits Epithelial-Mesenchymal Transformation and Promotes Apoptosis in Papillary Thyroid Carcinoma via miR-106a-5p/JAZF1 Axis.

机构信息

First Department of Thyroid Surgery, The Affiliated Hospital of Putian University, No. 999 Dongzhen East Road, Licheng District, Putian, 351100, Fujian, China.

出版信息

Biochem Genet. 2024 Dec;62(6):4755-4769. doi: 10.1007/s10528-024-10672-1. Epub 2024 Feb 15.

Abstract

Circular RNA ITCH (circ-ITCH) is implicated in papillary thyroid carcinoma (PTC) development. Nevertheless, the more detailed molecular mechanism remains uncovered. The transcriptional level of circ-ITCH was tested via quantitative real-time PCR. Transwell assay was introduced to assess the migrative and invasive abilities of cells. RNA interference technology was employed to reduce the level of circ-ITCH as well as JAZF1 in PTC cells. Western blot assay was utilized to reveal the content of JAZF1 and proteins related to epithelial-mesenchymal transformation (EMT) progression. Circ-ITCH was downregulated in PTC tissues as well as cells. Overexpression of circ-ITCH suppressed EMT, migration, invasion, facilitated apoptosis in PTC cells, while silencing circ-ITCH exhibited reversed effects. Additionally, miR-106a-5p was the target of circ-ITCH and negatively regulated through circ-ITCH. MiR-106a-5p mimic partly eliminated the influences of overexpressed circ-ITCH in PTC cells. Moreover, JAZF1 could interact with miR-106a-5p, then it was regulated via circ-ITCH. Silencing JAZF1 partially counteracted the role of circ-ITCH in PTC cells progress. This study uncovered that circ-ITCH suppressed the development of PTC cells at least partly by mediating miR-106a-5p/JAZF1 network.

摘要

环状 RNA ITCH(circ-ITCH)被认为与甲状腺乳头状癌(PTC)的发展有关。然而,其更详细的分子机制仍未被揭示。通过实时定量 PCR 检测 circ-ITCH 的转录水平。采用 Transwell 实验评估细胞的迁移和侵袭能力。利用 RNA 干扰技术降低 PTC 细胞中 circ-ITCH 和 JAZF1 的水平。Western blot 实验揭示 JAZF1 及与上皮间质转化(EMT)进展相关的蛋白含量。circ-ITCH 在 PTC 组织和细胞中下调。过表达 circ-ITCH 抑制 EMT、迁移、侵袭,促进 PTC 细胞凋亡,而沉默 circ-ITCH 则呈现相反的效果。此外,circ-ITCH 的靶标是 miR-106a-5p,通过 circ-ITCH 进行负调控。miR-106a-5p 模拟物部分消除了过表达 circ-ITCH 对 PTC 细胞的影响。此外,JAZF1 可以与 miR-106a-5p 相互作用,然后通过 circ-ITCH 进行调控。沉默 JAZF1 部分抵消了 circ-ITCH 在 PTC 细胞进展中的作用。本研究揭示,circ-ITCH 通过介导 miR-106a-5p/JAZF1 网络至少部分抑制 PTC 细胞的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d9a/11604786/fc41f5a60873/10528_2024_10672_Fig1_HTML.jpg

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