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微小 RNA-744 通过直接靶向 NOB1 抑制甲状腺乳头状癌细胞增殖和侵袭。

MicroRNA‑744 suppresses cell proliferation and invasion of papillary thyroid cancer by directly targeting NOB1.

机构信息

Department of General Surgery, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China.

Department of General Surgery, Yiyuan County People's Hospital, Zibo, Shandong 256199, P.R. China.

出版信息

Mol Med Rep. 2019 Mar;19(3):1903-1910. doi: 10.3892/mmr.2019.9826. Epub 2019 Jan 4.

DOI:10.3892/mmr.2019.9826
PMID:30628685
Abstract

MicroRNAs (miRs) serve important roles in the formation and progression of papillary thyroid cancer (PTC) by regulating numerous physiological and pathological behaviours. Thus, investigating the functional roles of specific miRNAs in PTC may contribute in identifying effective therapeutic targets for the management of patients with PTC. miR‑744 is emerging as a cancer‑associated miRNA in numerous types of human cancers; however, the expression and specific functions of miR‑744 in PTC are yet to be determined, and the mechanism underlying the regulatory roles of miR‑744 in PTC remains unknown. In the present study, miR‑744 expression was significantly decreased in PTC tissues and cell lines, as detected by reverse transcription‑quantitative polymerase chain reaction. miR‑744 restoration inhibited cell proliferation and invasion in PTC. Bioinformatics analysis predicted NIN1 (RPN12) binding protein 1 homolog (NOB1) as a potential target of miR‑744. Subsequent experiments validated NOB1 as a direct target gene of miR‑744 in PTC. Furthermore, NOB1 was upregulated in PTC tissues and negatively correlated with miR‑744 expression. NOB1 overexpression could counteract miR‑744‑mediated antitumor effects on PTC cells. In summary, these findings indicated that miR‑744 may inhibit the progression of PTC by directly targeting NOB1. The identification of the miR‑744/NOB1 axis may provide insight into potential targets for the treatment of patients with PTC and improve their prognosis.

摘要

微小 RNA(miRs)通过调节许多生理和病理行为,在甲状腺乳头状癌(PTC)的形成和进展中发挥重要作用。因此,研究特定 miRs 在 PTC 中的功能作用可能有助于确定治疗 PTC 患者的有效治疗靶点。miR-744 作为一种癌相关 miRNA,在多种人类癌症中都有出现;然而,miR-744 在 PTC 中的表达和特定功能尚未确定,miR-744 在 PTC 中的调控作用的机制仍不清楚。在本研究中,通过逆转录-定量聚合酶链反应检测到 miR-744 在 PTC 组织和细胞系中的表达明显降低。miR-744 恢复抑制 PTC 中的细胞增殖和侵袭。生物信息学分析预测 NIN1(RPN12)结合蛋白 1 同源物(NOB1)是 miR-744 的潜在靶标。随后的实验验证了 NOB1 是 PTC 中 miR-744 的直接靶基因。此外,NOB1 在 PTC 组织中上调,并与 miR-744 的表达呈负相关。NOB1 的过表达可以抵消 miR-744 对 PTC 细胞的抗肿瘤作用。综上所述,这些发现表明 miR-744 可能通过直接靶向 NOB1 抑制 PTC 的进展。鉴定 miR-744/NOB1 轴可能为治疗 PTC 患者提供潜在靶点,并改善其预后。

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