LncRNA NONHSAT114552 Sponges miR-320d to Promote Proliferation and Invasion of Chordoma Through Upregulating NRP1.

Kai Zhang,Kangwu Chen,Hao Liu,Zixiang Liu,Huilin Yang,Xiaofeng Shao,Yingchuang Tang,Xi Hua

doi:10.3389/fphar.2021.773918

Kai Zhang, Kangwu Chen + Show 6 more

Open Access

https://doi.org/10.3389/fphar.2021.773918

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Abstract

Chordoma is a relatively rare malignant bone tumor with high local recurrence. To date, the mechanism remains unclear. lncRNAs play a pivotal role in tumorigenesis by acting as competitive endogenous RNAs of microRNAs. However, the biological role of lncRNA is still unclear in chordoma. In this research, our aim is to investigate the roles and regulation mechanisms of lncRNA NONHSAT114552 in chordoma development. The expression level of NONHSAT114552 and miR-320d in chordoma tissues was determined by qRT-PCR. Meantime, the correlation between NONHSAT114552 and clinical prognosis was also studied. Bioinformatics analysis and luciferase reporter assays were used to verify the relationship between NONHSAT114552 and miR-320d, and between miR-320d and Neuropilin 1 (NRP1). In addition, effects of NONHSAT114552 on chordoma cells (U-CH1 and U-CH2) proliferation and invasion and its regulation on miR-320d were also evaluated. Furthermore, the influences of NONHSAT114552/miR-320d/NRP1 axis on chordoma tumorigenesis were investigated in vivo. NONHSAT114552 was overexpressed while miR-320d was down-regulated in chordoma tissue compared to fetal nucleus pulposus. Kaplan-Meier survival analysis showed that NONHSAT114552 overexpression was associated with patients’ poor prognosis. Knockdown of NONHSAT114552 significantly suppressed chordoma cell proliferation and invasion. In vitro studies confirmed that NONHSAT114552 acted as ceRNA to regulate NRP1 by directly sponging miR-320d, thus facilitating chordoma cell proliferation and invasion. In vivo study demonstrated that NONHSAT114552 moderated chordoma growth by sponging miR-320d to regulating NRP1. Our findings indicate that lncRNA NONHSAT114552 exhibits a critical role in the tumorigenesis and development of chordoma and it may become one potential prognostic marker and therapeutic target for this disease. .

Highlights

Chordoma is a rarely primary malignant bone tumor, which is believed to originate from embryonic residual notochord tissue (Denaro et al, 2020)
LncRNA NONHSAT114552 Is Up-Regulated While miR-320d Is Down-Regulated in Chordoma
Compared to fetal nucleus pulposus (FNP), Quantitative Real-Time PCR (qRT-PCR) showed that NONHSAT114552 was significantly up-regulated while miR-320d was down-regulated in chordoma tissues (Figures 1A,B)

Summary

Introduction

Chordoma is a rarely primary malignant bone tumor, which is believed to originate from embryonic residual notochord tissue (Denaro et al, 2020). Many patients suffer local recurrence and metastasis even if they have received complete tumor resection. It is reported that local recurrence rate is as high as 30–85%, and the postoperative local recurrence rate is considered to be the most important predictor of death (Chen et al, 2011; Kayani et al, 2014; Ruosi et al, 2015; Denaro et al, 2020). Through the preliminary clinical studies, we have found that local recurrence of chordoma is partly related to the invasive nature of the tumor itself (Chen et al, 2011; Zhang et al, 2014a). There are many studies on the mechanism of chordoma recurrence and important progress has been made, the pathogenesis of chordoma is still unclear, ideal and effective therapeutic target has not been found yet

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