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OTUD6B-AS1 通过靶向 miR-183-5p 和 miR-21 抑制甲状腺癌细胞的活力、迁移和侵袭。

OTUD6B-AS1 Inhibits Viability, Migration, and Invasion of Thyroid Carcinoma by Targeting miR-183-5p and miR-21.

机构信息

Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.

出版信息

Front Endocrinol (Lausanne). 2020 Mar 17;11:136. doi: 10.3389/fendo.2020.00136. eCollection 2020.

Abstract

The long noncoding RNA (lncRNA) functions as a regulator of initiation, progression, and metastasis of thyroid carcinomas. lncRNA OTUD6B antisense RNA 1 (OTUD6B-AS1) is a tumor-suppressive noncoding RNA in clear cell renal cell carcinoma. The role of OTUD6B-AS1 in thyroid carcinomas has not been reported yet. We aim to investigate the expression and biological functions of OTUD6B-AS1 in thyroid carcinomas. The expression level of OTUD6B-AS1 was measured in 60 paired human thyroid carcinoma tissues and corresponding adjacent normal thyroid tissues. The correlations between the OTUD6B-AS1 expression levels and clinicopathological features were evaluated using the Mann-Whitney test. The effects of OTUD6B-AS1 on thyroid carcinoma cells were determined via the MTT and transwell assays. The potential targets of OTUD6B-AS1 were screened using the online programs OncomiR and StarBase 3.0, and the LncBase Predicted v.2. Luciferase reporter assay was used to confirm the interactions between OTUD6B-AS1 and its potential targets. OTUD6B-AS1 was downregulated in thyroid carcinoma tissue samples. The expression of OTUD6B-AS1 correlated with tumor size, clinical stage, and lymphatic metastasis of thyroid carcinoma. Overexpression of OTUD6B-AS1 significantly decreased the viability, migration, and invasion of thyroid carcinoma cells. Online programs predicted miR-183-5p and miR-21 as potential targets of OTUD6B-AS1. Luciferase reporter assays showed miR-183-5p and miR-21 bound to OTUD6B-AS1. Moreover, overexpression of miR-183-5p and miR-21 compromised the inhibitory effects of OTUD6B-AS1 on viability, migration, and invasion of thyroid carcinoma cells. Taken together, our findings present evidence of lncRNA OTUD6B-AS1 as a tumor suppressor in thyroid carcinomas. OTUD6B-AS1 inhibits viability, migration, and invasion of thyroid carcinoma by targeting miR-183-5p and miR-21.

摘要

长链非编码 RNA(lncRNA)作为甲状腺癌发生、进展和转移的调节剂。lncRNA OTUD6B 反义 RNA 1(OTUD6B-AS1)在肾透明细胞癌中是一种肿瘤抑制性非编码 RNA。OTUD6B-AS1 在甲状腺癌中的作用尚未有报道。我们旨在研究 OTUD6B-AS1 在甲状腺癌中的表达和生物学功能。我们测量了 60 对人甲状腺癌组织和相应的癌旁正常甲状腺组织中 OTUD6B-AS1 的表达水平。采用 Mann-Whitney 检验评估 OTUD6B-AS1 表达水平与临床病理特征的相关性。通过 MTT 和 Transwell 测定评估 OTUD6B-AS1 对甲状腺癌细胞的影响。使用在线程序 OncomiR 和 StarBase 3.0 筛选 OTUD6B-AS1 的潜在靶标,并使用 LncBase Predicted v.2. 荧光素酶报告试验来验证 OTUD6B-AS1 与其潜在靶标的相互作用。OTUD6B-AS1 在甲状腺癌组织样本中下调。OTUD6B-AS1 的表达与甲状腺癌的肿瘤大小、临床分期和淋巴转移相关。OTUD6B-AS1 的过表达显著降低甲状腺癌细胞的活力、迁移和侵袭。在线程序预测 miR-183-5p 和 miR-21 是 OTUD6B-AS1 的潜在靶标。荧光素酶报告试验表明 miR-183-5p 和 miR-21 与 OTUD6B-AS1 结合。此外,miR-183-5p 和 miR-21 的过表达削弱了 OTUD6B-AS1 对甲状腺癌细胞活力、迁移和侵袭的抑制作用。综上所述,我们的研究结果表明 lncRNA OTUD6B-AS1 是甲状腺癌的肿瘤抑制因子。OTUD6B-AS1 通过靶向 miR-183-5p 和 miR-21 抑制甲状腺癌细胞的活力、迁移和侵袭。

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