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circ_NEK6 敲低通过调控 miR-370-3p/MYH9 轴降低分化型甲状腺癌细胞的碘抵抗。

Knockdown of circ_NEK6 Decreased I Resistance of Differentiated Thyroid Carcinoma via Regulating miR-370-3p/MYH9 Axis.

机构信息

Department of Nuclear Medicine, Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University, Yunnan, China.

Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Yunnan, China.

出版信息

Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211004950. doi: 10.1177/15330338211004950.

DOI:10.1177/15330338211004950
PMID:33759638
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8093613/
Abstract

Radioresistance is a crucial factor for the failure of iodine 131 (I)-based radiotherapy for differentiated thyroid carcinoma (DTC). This study aimed to explore the effect of circ_NEK6 on the development of I resistance in DTC and its potential mechanism. In this study, we demonstrated that circ_NEK6 expression was significantly elevated in I-resistant DTC tissues and cell lines. Knockdown of circ_NEK6 significantly repressed I resistance via inhibiting cell proliferation, migration, invasion abilities, and inducing cell apoptosis and DNA damage in I-resistant DTC cells. Mechanistically, knockdown of circ_NEK6 suppressed I resistance in DTC by upregulating the inhibitory effect of miR-370-3p on the expression of myosin heavy chain 9 (MYH9). experiments showed that circ_NEK6 inhibition aggravated I radiation-induced inhibition of xenograft tumor growth. Taken together, knockdown of circ_NEK6 repressed I resistance in DTC cells by regulating the miR-370-3p/MYH9 axis, indicating that circ_NEK6 may act as a potential biomarker and therapeutic target for DTC patients with I resistance.

摘要

放射性抵抗是碘 131（I）为基础的分化型甲状腺癌（DTC）放疗失败的关键因素。本研究旨在探讨 circ_NEK6 对 DTC 碘抵抗发展的影响及其潜在机制。在这项研究中，我们表明 circ_NEK6 在碘抵抗性 DTC 组织和细胞系中表达显著上调。circ_NEK6 的敲低通过抑制细胞增殖、迁移、侵袭能力，以及诱导碘抵抗性 DTC 细胞凋亡和 DNA 损伤，显著抑制碘抵抗。在机制上，circ_NEK6 的敲低通过上调 miR-370-3p 对肌球蛋白重链 9（MYH9）表达的抑制作用，抑制 DTC 中的碘抵抗。体内实验表明，circ_NEK6 抑制可加重碘照射诱导的异种移植肿瘤生长抑制。综上所述，circ_NEK6 的敲低通过调节 miR-370-3p/MYH9 轴抑制 DTC 细胞的碘抵抗，表明 circ_NEK6 可能是碘抵抗的 DTC 患者的潜在生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7929/8093613/b770c42092bb/10.1177_15330338211004950-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7929/8093613/34c5ecf239ad/10.1177_15330338211004950-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7929/8093613/bcb0617b08bc/10.1177_15330338211004950-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7929/8093613/7d8d9908d3d2/10.1177_15330338211004950-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7929/8093613/d9c3ab009ce5/10.1177_15330338211004950-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7929/8093613/3b4f7f10cafb/10.1177_15330338211004950-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7929/8093613/b770c42092bb/10.1177_15330338211004950-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7929/8093613/34c5ecf239ad/10.1177_15330338211004950-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7929/8093613/bcb0617b08bc/10.1177_15330338211004950-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7929/8093613/7d8d9908d3d2/10.1177_15330338211004950-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7929/8093613/d9c3ab009ce5/10.1177_15330338211004950-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7929/8093613/3b4f7f10cafb/10.1177_15330338211004950-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7929/8093613/b770c42092bb/10.1177_15330338211004950-fig6.jpg

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