HYPOXIA induces lncRNA HOTAIR for recruiting RELA in papillary thyroid cancer cells to upregulate miR-181a and promote angiogenesis.

IF 5.4 2区医学 Q1 Medicine Journal of Endocrinological Investigation Pub Date : 2024-11-01 Epub Date: 2024-05-15 DOI:10.1007/s40618-024-02388-1

J Lu, X Liu, A Cen, Y Hong, Y Wang

{"title":"HYPOXIA induces lncRNA HOTAIR for recruiting RELA in papillary thyroid cancer cells to upregulate miR-181a and promote angiogenesis.","authors":"J Lu, X Liu, A Cen, Y Hong, Y Wang","doi":"10.1007/s40618-024-02388-1","DOIUrl":null,"url":null,"abstract":"Background: Papillary thyroid carcinoma (PTC) is one of the most common subtypes of thyroid carcinoma. Exosomal miR-181a plays an important role in the development of PTC. This study examined the regulatory mechanism of miR-181a under conditions of hypoxia and its impact on angiogenesis.Methods: A ribonucleoprotein immunoprecipitation (RIP) experiment was conducted to verify the interaction between HOTAIR and RELA. The relationship between RELA and the miR-181a promoter was detected by ChIP-qPCR. Short hairpin (sh) RNA was designed to knock down HOTAIR in TPC cells. The underlying mechanism of miR-181a was verified by use of dual-luciferase assays and rescue experiments. The regulatory effect of GATA6 on angiogenesis was studied using CCK8, EdU, Transwell, and western blot assays.Results: A RIP assay showed that HOTAIR could bind to RELA under hypoxic conditions. ChIP-qPCR and dual luciferase assays showed RELA could interact with the miR181a promoter and upregulate miR-181a. Knockdown of HOTAIR downregulated miR-181a in TPC-1 cells, and the downregulation could be rescued by RELA overexpression. MiR-181a downregulated GATA6 in HUVEC cells. Overexpression of GATA6 inhibited HUVEC proliferation, migration, tube formation, and EGFR expression. Exosomal miR-181a promoted angiogenesis by downregulating GATA6 expression.Conclusion: HOTAIR activated RELA to upregulate miR-181a during hypoxia. Exosomal miR-181a promotes tumor angiogenesis by downregulating GATA6.","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":null,"pages":null},"PeriodicalIF":5.4000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Endocrinological Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40618-024-02388-1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/15 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Papillary thyroid carcinoma (PTC) is one of the most common subtypes of thyroid carcinoma. Exosomal miR-181a plays an important role in the development of PTC. This study examined the regulatory mechanism of miR-181a under conditions of hypoxia and its impact on angiogenesis.

Methods: A ribonucleoprotein immunoprecipitation (RIP) experiment was conducted to verify the interaction between HOTAIR and RELA. The relationship between RELA and the miR-181a promoter was detected by ChIP-qPCR. Short hairpin (sh) RNA was designed to knock down HOTAIR in TPC cells. The underlying mechanism of miR-181a was verified by use of dual-luciferase assays and rescue experiments. The regulatory effect of GATA6 on angiogenesis was studied using CCK8, EdU, Transwell, and western blot assays.

Results: A RIP assay showed that HOTAIR could bind to RELA under hypoxic conditions. ChIP-qPCR and dual luciferase assays showed RELA could interact with the miR181a promoter and upregulate miR-181a. Knockdown of HOTAIR downregulated miR-181a in TPC-1 cells, and the downregulation could be rescued by RELA overexpression. MiR-181a downregulated GATA6 in HUVEC cells. Overexpression of GATA6 inhibited HUVEC proliferation, migration, tube formation, and EGFR expression. Exosomal miR-181a promoted angiogenesis by downregulating GATA6 expression.

Conclusion: HOTAIR activated RELA to upregulate miR-181a during hypoxia. Exosomal miR-181a promotes tumor angiogenesis by downregulating GATA6.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

HYPOXIA诱导lncRNA HOTAIR招募甲状腺乳头状癌细胞中的RELA，从而上调miR-181a并促进血管生成。

背景：甲状腺乳头状癌（PTC）是甲状腺癌最常见的亚型之一。外泌体miR-181a在PTC的发展过程中起着重要作用。本研究探讨了缺氧条件下miR-181a的调控机制及其对血管生成的影响：方法：通过核糖核蛋白免疫沉淀（RIP）实验验证了HOTAIR与RELA之间的相互作用。通过 ChIP-qPCR 检测 RELA 与 miR-181a 启动子之间的关系。设计了短发夹（sh）RNA 来敲除 TPC 细胞中的 HOTAIR。利用双荧光素酶测定和拯救实验验证了 miR-181a 的内在机制。利用 CCK8、EdU、Transwell 和 Western 印迹实验研究了 GATA6 对血管生成的调控作用：RIP试验表明，在缺氧条件下，HOTAIR能与RELA结合。ChIP-qPCR和双荧光素酶检测表明，RELA能与miR181a启动子相互作用并上调miR-181a。敲除 HOTAIR 会下调 TPC-1 细胞中的 miR-181a，而 RELA 的过表达可以挽救这种下调。MiR-181a 下调了 HUVEC 细胞中的 GATA6。过表达 GATA6 可抑制 HUVEC 的增殖、迁移、管形成和表皮生长因子受体的表达。外泌体 miR-181a 通过下调 GATA6 的表达促进血管生成：结论：缺氧时，HOTAIR 激活 RELA 上调 miR-181a。外泌体miR-181a通过下调GATA6促进肿瘤血管生成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Journal of Endocrinological Investigation ENDOCRINOLOGY & METABOLISM-

CiteScore

8.10

自引率

7.40%

发文量

242

期刊介绍： The Journal of Endocrinological Investigation is a well-established, e-only endocrine journal founded 36 years ago in 1978. It is the official journal of the Italian Society of Endocrinology (SIE), established in 1964. Other Italian societies in the endocrinology and metabolism field are affiliated to the journal: Italian Society of Andrology and Sexual Medicine, Italian Society of Obesity, Italian Society of Pediatric Endocrinology and Diabetology, Clinical Endocrinologists’ Association, Thyroid Association, Endocrine Surgical Units Association, Italian Society of Pharmacology.