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环状 RNA 甘露糖苷酶 alpha 类 1A 成员 2 通过吸收 microRNA-449a 上调 metadherin 促进甲状腺乳头状癌细胞的增殖和迁移。

circRNA mannosidase alpha class 1A member 2 contributes to the proliferation and motility of papillary thyroid cancer cells through upregulating metadherin via absorbing microRNA-449a.

机构信息

School of Clinical Medicine, Jiamusi University and Departments of.

Medicine.

出版信息

Anticancer Drugs. 2023 Jan 1;34(1):44-56. doi: 10.1097/CAD.0000000000001340. Epub 2022 Aug 31.

DOI:10.1097/CAD.0000000000001340
PMID:36066401
Abstract

Papillary thyroid carcinoma (PTC) is a common malignancy in endocrine system globally. Accumulating articles have found that circular RNAs (circRNAs) were dysregulated, and they were involved in PTC development. The aim of this project was to explore the function and associated mechanism of circRNA mannosidase alpha class 1A member 2 (circMAN1A2) in PTC progression. The expression of RNA was determined by real-time quantitative PCR. Cell proliferation ability was analyzed by colony formation assay and 5-ethynyl-2'-deoxyuridine assay. Cell migration and invasion were assessed by wound healing assay and transwell invasion assay, respectively. Protein levels were determined by Western blot assay. Dual-luciferase reporter assay and RNA immunoprecipitation assay were applied to confirm the interaction between microRNA-449a (miR-449a) and circMAN1A2 or metadherin (MTDH). Xenograft tumor model was utilized to explore the effect of circMAN1A2 silencing on tumor growth in vivo . CircMAN1A2 expression was elevated in PTC specimens and three PTC cell lines relative to adjacent normal specimens and Nthy-ori 3-1 cell line. CircMAN1A2 silencing inhibited the proliferation and motility of PTC cells. CircMAN1A2 acted as a molecular sponge of miR-449a, and circMAN1A2 knockdown suppressed PTC development partly through upregulating miR-449a. MiR-449a bound to the 3' untranslated region of MTDH, and miR-449a restrained PTC progression partly through down-regulating MTDH. CircMAN1A2 interference suppressed PTC progression in vivo . CircMAN1A2 contributed to the proliferation ability and motility of PTC cells through enhancing MTDH expression via sponging miR-449a.

摘要

甲状腺乳头状癌 (PTC) 是全球内分泌系统中常见的恶性肿瘤。越来越多的文章发现,环状 RNA (circRNA) 表达失调,并且它们参与了 PTC 的发生发展。本项目旨在探讨甘露糖苷酶 α 类 1A 成员 2 环状 RNA (circMAN1A2) 在 PTC 进展中的作用及其相关机制。通过实时定量 PCR 测定 RNA 的表达。通过集落形成试验和 5-乙炔基-2'-脱氧尿苷试验分析细胞增殖能力。通过划痕愈合试验和 Transwell 侵袭试验分别评估细胞迁移和侵袭能力。通过 Western blot 测定蛋白水平。应用双荧光素酶报告基因检测和 RNA 免疫沉淀试验证实 microRNA-449a (miR-449a) 与 circMAN1A2 或间皮素 (MTDH) 之间的相互作用。利用异种移植肿瘤模型探讨沉默 circMAN1A2 对体内肿瘤生长的影响。与相邻正常标本和 Nthy-ori 3-1 细胞系相比,PTC 标本和三种 PTC 细胞系中 circMAN1A2 的表达升高。沉默 circMAN1A2 抑制 PTC 细胞的增殖和迁移。circMAN1A2 作为 miR-449a 的分子海绵,circMAN1A2 下调部分通过上调 miR-449a 抑制 PTC 的发生发展。miR-449a 结合 MTDH 的 3'非翻译区,miR-449a 通过下调 MTDH 部分抑制 PTC 的进展。沉默 circMAN1A2 抑制体内 PTC 的进展。circMAN1A2 通过海绵 miR-449a 增强 MTDH 表达促进 PTC 细胞的增殖能力和迁移能力。

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