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NEAT1 的表达水平通过调节 NEAT1/miR-9/PTEN 和 NEAT1/miR-124/PDCD6 信号通路来区分良性和恶性甲状腺结节。

Expression level of NEAT1 differentiates benign and malignant thyroid nodules by regulating NEAT1/miR‑9/PTEN and NEAT1/miR‑124/PDCD6 signalling.

机构信息

Department of Ultrasound, Southwest University Hospital, Chongqing 400715, P.R. China.

Department of Abdominal Ultrasound, Xinjiang Autonomous Region Hospital of Traditional Chinese Medicine, Urumchi, Xinjiang 830000, P.R. China.

出版信息

Int J Mol Med. 2020 Nov;46(5):1661-1670. doi: 10.3892/ijmm.2020.4721. Epub 2020 Sep 4.

DOI:10.3892/ijmm.2020.4721
PMID:32901835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7521579/
Abstract

The incidence of thyroid nodules has been increasing worldwide; however, there are currently no feasible and robust methods to differentiate malignant thyroid nodules from benign thyroid nodules. The present study aimed to establish a practical method to determine the malignancy of thyroid nodules. Reverse transcription‑quantitative PCR and western blot analyses were performed to compare the levels of long non‑coding RNA nuclear enriched abundant transcript 1 (NEAT1), microRNA (miR)‑9, miR‑124, PTEN and programmed cell death protein 6 (PDCD6) in the peripheral blood and thyroid tissue samples between patients with malignant and benign thyroid nodules. Additionally, a regulatory relationship between NEAT1, miR‑124, miR‑9, PTEN and PDCD6 was established in the present study. The diagnostic value of NEAT1, miR‑124 and miR‑9 was determined using a ROC analysis. The expression levels of NEAT1, PTEN and PDCD6 in peripheral blood and thyroid tissue samples collected from the benign group were higher compared with those in the malignant group, whereas the expression levels of miR‑124 and miR‑9 were lower in the benign group. In the peripheral blood, NEAT1 expression exhibited an area under the curve (AUC) value of 0.8546, whereas miR‑124 and miR‑9 expression had AUC values of 0.7657 and 0.7019, respectively. In the thyroid tissue, NEAT1, miR‑124, and miR‑9 had AUC values of 0.9304, 0.8221 and 0.7757, respectively. Additionally, miR‑9 and miR‑124 expression levels in BCPaP and SW579 cells was decreased after transfection with a NEAT1 expression vector compared with those in cells transfected with the control vector, whereas the expression of PTEN and PDCD6 was upregulated. By contrast, transfection with short hairpin RNA targeting NEAT1 notably increased the expression of miR‑9 and miR‑124 while downregulating the expression of PTEN and PDCD6 compared with that in the control cells. In conclusion, the results of the present study demonstrated that the dysregulation of NEAT1 expression may be used to differentiate benign and malignant thyroid nodules.

摘要

甲状腺结节的发病率在全球范围内呈上升趋势;然而,目前尚无可行且稳健的方法来区分恶性甲状腺结节和良性甲状腺结节。本研究旨在建立一种实用的方法来确定甲状腺结节的恶性程度。通过逆转录-定量 PCR 和 Western blot 分析比较了恶性和良性甲状腺结节患者外周血和甲状腺组织样本中长链非编码 RNA 核富集丰富转录物 1(NEAT1)、微小 RNA(miR)-9、miR-124、PTEN 和程序性细胞死亡蛋白 6(PDCD6)的水平。此外,本研究还建立了 NEAT1、miR-124、miR-9、PTEN 和 PDCD6 之间的调控关系。通过 ROC 分析确定了 NEAT1、miR-124 和 miR-9 的诊断价值。与恶性组相比,良性组外周血和甲状腺组织样本中 NEAT1、PTEN 和 PDCD6 的表达水平较高,而 miR-124 和 miR-9 的表达水平较低。在外周血中,NEAT1 表达的 AUC 值为 0.8546,而 miR-124 和 miR-9 的 AUC 值分别为 0.7657 和 0.7019。在甲状腺组织中,NEAT1、miR-124 和 miR-9 的 AUC 值分别为 0.9304、0.8221 和 0.7757。此外,与转染对照载体的细胞相比,转染 NEAT1 表达载体后 BCPaP 和 SW579 细胞中 miR-9 和 miR-124 的表达水平降低,而 PTEN 和 PDCD6 的表达水平上调。相反,与对照细胞相比,靶向 NEAT1 的短发夹 RNA 转染显著增加了 miR-9 和 miR-124 的表达,同时下调了 PTEN 和 PDCD6 的表达。综上所述,本研究结果表明,NEAT1 表达的失调可用于区分良性和恶性甲状腺结节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/33e9ab622a8f/IJMM-46-05-1661-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/f4d8f186e702/IJMM-46-05-1661-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/f8d06382e35a/IJMM-46-05-1661-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/9c009d5cfaab/IJMM-46-05-1661-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/5ed426e54021/IJMM-46-05-1661-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/c1d9bebc26aa/IJMM-46-05-1661-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/c5903fee447e/IJMM-46-05-1661-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/33e9ab622a8f/IJMM-46-05-1661-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/f4d8f186e702/IJMM-46-05-1661-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/f8d06382e35a/IJMM-46-05-1661-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/9c009d5cfaab/IJMM-46-05-1661-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/5ed426e54021/IJMM-46-05-1661-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/c1d9bebc26aa/IJMM-46-05-1661-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/c5903fee447e/IJMM-46-05-1661-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6732/7521579/33e9ab622a8f/IJMM-46-05-1661-g06.jpg

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