长非编码RNA MFSD4A-AS1促进癌症甲状腺乳头状癌的淋巴管生成和淋巴转移。

IF 4.1 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Endocrine-related cancer Pub Date : 2023-02-08 Print Date: 2023-03-01 DOI:10.1530/ERC-22-0221
Xiaoli Liu, Chunhai Zhang, Xiaomiao Wang, Can Cui, Hanwen Cui, Baishu Zhu, Anqi Chen, Lu Zhang, Jingwei Xin, Qingfeng Fu, Gianlorenzo Dionigi, Hui Sun
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引用次数: 2

摘要

淋巴转移是导致癌症(PTC)复发和进展的主要原因,其中长非编码RNA(lncRNA)的失调已被广泛证明与之有关。然而,PTC中与淋巴结转移相关的特定lncRNA尚未确定。在癌症基因组图谱的PTC数据集和我们的临床样本中探索了淋巴结转移相关lncRNA MFSD4A-AS1。在体外和体内研究了MFSD4A-AS1在淋巴结转移中的作用。通过生物信息学分析、荧光素酶测定和RNA免疫沉淀测定来确定MFSD4A-AS1在PTC淋巴转移中的潜在靶点和潜在途径。MFSD4A-AS1在伴有淋巴结转移的PTC组织中特异性上调。上调MFSD4A-AS1促进人脐静脉内皮细胞的网状物形成和迁移以及PTC细胞的侵袭和迁移。重要且一致的是,MFSD4A-AS1通过诱导淋巴管生成和增强PTC细胞的侵袭能力,在体内促进PTC细胞的淋巴转移。机制分析进一步表明,MFSD4A-AS1作为竞争性内源性RNA,螯合miR-30c-2-3p、miR-145-3p和miR-139-5p,破坏miRNA介导的对血管内皮生长因子A和C的抑制,并通过吸收靶向TGFBR2和USP15的miR-30c-2-3 p,进一步激活转化生长因子(TGF)-β信号传导,两者协同促进PTC的淋巴管生成和淋巴转移。我们的研究结果揭示了MFSD4A-AS1促进PTC淋巴转移的新的双重机制,这将促进PTC抗淋巴转移治疗策略的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Long non-coding RNA MFSD4A-AS1 promotes lymphangiogenesis and lymphatic metastasis of papillary thyroid cancer.

Long non-coding RNA MFSD4A-AS1 promotes lymphangiogenesis and lymphatic metastasis of papillary thyroid cancer.

Long non-coding RNA MFSD4A-AS1 promotes lymphangiogenesis and lymphatic metastasis of papillary thyroid cancer.

Long non-coding RNA MFSD4A-AS1 promotes lymphangiogenesis and lymphatic metastasis of papillary thyroid cancer.

Lymphatic metastasis is the leading cause responsible for recurrence and progression in papillary thyroid cancer (PTC), where dysregulation of long non-coding RNAs (lncRNAs) has been extensively demonstrated to be implicated. However, the specific lymphatic node metastatsis-related lncRNAs remain not identified in PTC yet. Lymphatic node metastatsis-related lncRNA, MFSD4A-AS1, was explored in the PTC dataset from The Cancer Genome Atlas and our clinical samples. The roles of MFSD4A-AS1 in lymphatic metastasis were investigated in vitro and in vivo. Bioinformatic analysis, luciferase assay and RNA immunoprecipitation assay were performed to identify the potential targets and the underlying pathway of MFSD4A-AS1 in lymphatic metastasis of PTC. MFSD4A-AS1 was specifically upregulated in PTC tissues with lymphatic metastasis. Upregulating MFSD4A-AS1 promoted mesh formation and migration of human umbilical vein endothelial cells and invasion and migration of PTC cells. Importantly and consistently, MFSD4A-AS1 promoted lymphatic metastasis of PTC cells in vivo by inducing the lymphangiogenic formation and enhancing the invasive capability of PTC cells. Mechanistic dissection further revealed that MFSD4A-AS1 functioned as competing endogenous RNA to sequester miR-30c-2-3p, miR-145-3p and miR-139-5p to disrupt the miRNA-mediated inhibition of vascular endothelial growth factors A and C, and further activated transforming growth factor (TGF)-β signaling by sponging miR-30c-2-3p that targeted TGFBR2 and USP15, both of which synergistically promoted lymphangiogenesis and lymphatic metastasis of PTC. Our results unravel novel dual mechanisms by which MFSD4A-AS1 promotes lymphatic metastasis of PTC, which will facilitate the development of anti-lymphatic metastatic therapeutic strategy in PTC.

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来源期刊
Endocrine-related cancer
Endocrine-related cancer 医学-内分泌学与代谢
CiteScore
7.80
自引率
2.60%
发文量
138
审稿时长
6-12 weeks
期刊介绍: Endocrine-Related Cancer is an official flagship journal of the Society for Endocrinology and is endorsed by the European Society of Endocrinology, the United Kingdom and Ireland Neuroendocrine Society, and the Japanese Hormones and Cancer Society. Endocrine-Related Cancer provides a unique international forum for the publication of high quality original articles describing novel, cutting edge basic laboratory, translational and clinical investigations of human health and disease focusing on endocrine neoplasias and hormone-dependent cancers; and for the publication of authoritative review articles in these topics. Endocrine neoplasias include adrenal cortex, breast, multiple endocrine neoplasia, neuroendocrine tumours, ovary, prostate, paraganglioma, parathyroid, pheochromocytoma pituitary, testes, thyroid and hormone-dependent cancers. Neoplasias affecting metabolism and energy production such as bladder, bone, kidney, lung, and head and neck, are also considered.
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