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长链非编码 RNA NEAT1 通过调控 miR-365/RGS20 促进口腔鳞状细胞癌的增殖和侵袭。

lncRNA NEAT1 promotes cell proliferation and invasion by regulating miR‑365/RGS20 in oral squamous cell carcinoma.

机构信息

Department of Stomatology, General Hospital of Benxi Iron and Steel Co., Ltd., Benxi, Liaoning 111700, P.R. China.

Department of Scientific Research and Medical Education Management, General Hospital of Benxi Iron and Steel Co., Ltd., Benxi, Liaoning 111700, P.R. China.

出版信息

Oncol Rep. 2018 Apr;39(4):1948-1956. doi: 10.3892/or.2018.6283. Epub 2018 Feb 26.

Abstract

Long non‑coding RNAs (lncRNAs) have emerged as critical regulators of tumor progression. However, the function and mechanism of lncRNA NEAT1 in oral squamous cell carcinoma (OSCC) are unclear. In the present study, NEAT1 was significantly upregulated in OSCC cells and tissues. High expression of NEAT1 was correlated with advanced TNM stage and poor survival of patients. Using bioinformatics prediction and experimental analysis, we determined that NEAT1 could negatively regulate the expression of miR‑365. The expression of miR‑365 was decreased in OSCC tissues and inversely correlated with NEAT1 in tumors. Functionally, knockdown of NEAT1 significantly inhibited cell proliferation and invasion and induced cell cycle arrest at the G0/G1 phase and apoptosis, whereas inhibition of miR‑365 abolished the suppressive effect of NEAT1 knockdown on cellular processes. RGS20, a direct target of miR‑365, could reverse the tumor suppressive role of miR‑365 mimic by enhancing cell viability and motility. Moreover, the protein levels of RGS20, cyclin D1, E‑cadherin, N‑cadherin and vimentin could be regulated by the NEAT1/miR‑365 axis. NEAT1 silencing also inhibited tumor growth in vivo. Collectively, we revealed that the NEAT1/miR‑365/RGS20 axis may be a novel mechanism or therapeutic strategy for OSCC treatment.

摘要

长链非编码 RNA(lncRNA)已成为肿瘤进展的关键调控因子。然而,lncRNA NEAT1 在口腔鳞状细胞癌(OSCC)中的功能和机制尚不清楚。在本研究中,NEAT1 在 OSCC 细胞和组织中显著上调。NEAT1 的高表达与 TNM 晚期和患者不良生存相关。通过生物信息学预测和实验分析,我们确定 NEAT1 可以负调控 miR-365 的表达。miR-365 在 OSCC 组织中的表达降低,与肿瘤中的 NEAT1 呈负相关。功能上,敲低 NEAT1 可显著抑制细胞增殖和侵袭,并诱导细胞周期停滞在 G0/G1 期和细胞凋亡,而抑制 miR-365 则消除了 NEAT1 敲低对细胞过程的抑制作用。RGS20 是 miR-365 的直接靶标,通过增强细胞活力和运动能力,可以逆转 miR-365 模拟物的肿瘤抑制作用。此外,RGS20、细胞周期蛋白 D1、E-钙黏蛋白、N-钙黏蛋白和波形蛋白的蛋白水平可以通过 NEAT1/miR-365 轴进行调节。NEAT1 沉默也抑制了体内肿瘤的生长。综上所述,我们揭示了 NEAT1/miR-365/RGS20 轴可能是 OSCC 治疗的一种新的机制或治疗策略。

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