长链非编码 RNA-NONHSAT024778 通过调控 miR-1290/Robo1 轴促进脊索瘤细胞的增殖和侵袭。

LncRNA-NONHSAT024778 promote the proliferation and invasion of chordoma cell by regulating miR-1290/Robo1 axis.

机构信息

Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, China.

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

出版信息

Int J Biol Sci. 2021 Feb 8;17(3):796-806. doi: 10.7150/ijbs.54091. eCollection 2021.

Abstract

Chordoma is a malignant bone tumor originating from the embryonic remnants of the notochord. lncRNAs act as competing endogenous RNAs (ceRNAs) and play a critical role in tumor pathology. However, the biological role of lncRNA-NONHSAT024778 and the underlying molecular mechanism in chordoma remains unknown. qRT-PCR was used to analyze the expression changes of NONHSAT024778 and miR-1290 in chordoma tissues and cell lines. Bioinformatics analysis and luciferase reporter assay were applied to detect the targeting binding effect between NONHSAT024778 and miR-1290, and between Robo1 and miR-1290. The effect of NONHSAT024778 on chordoma cell proliferation and invasion and its regulation of miR-1290 by acting as a ceRNA were also investigated. An increased NONHSAT024778 expression was correlated with a decreased miR-1290 level in chordoma tissues. NONHSAT024778 knockdown suppressed the proliferation and invasion of chordoma cells. miR-1290 restored expression rescued the carcinogenic function of NONHSAT024778. Bioinformatics analysis showed that NONHSAT024778 acted as ceRNA to regulate Robo1 via sponging miR-1290 in chordoma cells, thereby promoting chordoma cell malignant progression. results confirmed the anti-tumor effects of NONHSAT024778 knockdown activating miR-1290 to inhibit the oncogene Robo1. NONHSAT024778 is substantially overexpressed, whereas miR-1290 is decreased in chordoma tissue. NONHSAT024778-miR-1290-Robo1 axis plays a critical role in chordoma tumorigenesis and might be a potential predictive biomarker for the diagnosis and therapeutic target among patients with chordoma.

摘要

脊索瘤是一种起源于脊索胚胎残余物的恶性骨肿瘤。lncRNAs 作为竞争性内源 RNA(ceRNA)发挥作用,在肿瘤病理学中发挥关键作用。然而,lncRNA-NONHSAT024778 在脊索瘤中的生物学作用及其潜在的分子机制尚不清楚。qRT-PCR 用于分析 NONHSAT024778 和 miR-1290 在脊索瘤组织和细胞系中的表达变化。生物信息学分析和荧光素酶报告基因检测用于检测 NONHSAT024778 和 miR-1290 之间、Robo1 和 miR-1290 之间的靶向结合效应。还研究了 NONHSAT024778 对脊索瘤细胞增殖和侵袭的影响,以及通过作为 ceRNA 调节 miR-1290 的作用。NONHSAT024778 的表达增加与脊索瘤组织中 miR-1290 水平的降低相关。NONHSAT024778 敲低抑制了脊索瘤细胞的增殖和侵袭。miR-1290 恢复表达挽救了 NONHSAT024778 的致癌功能。生物信息学分析表明,NONHSAT024778 在脊索瘤细胞中作为 ceRNA 通过海绵吸附 miR-1290 来调节 Robo1,从而促进脊索瘤细胞的恶性进展。结果证实了 NONHSAT024778 敲低通过激活 miR-1290 抑制致癌基因 Robo1 的抗肿瘤作用。NONHSAT024778 在脊索瘤组织中大量过表达,而 miR-1290 则减少。NONHSAT024778-miR-1290-Robo1 轴在脊索瘤肿瘤发生中起关键作用,可能是脊索瘤患者诊断和治疗靶点的潜在预测生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac7c/7975704/0229878e646d/ijbsv17p0796g001.jpg

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