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

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. .

Blocking CCR10 Expression Activates m6A Methylation and Alleviates Vascular Endothelial Cell Injury

“…Therefore, to confirm the relationship between CCR10 and m6A, we detected the CCR10 expression by qRT-PCR and found elevated CCR10 expression levels in damaged HDMECs, confirming the above RNA-Seq results. m6A methylation was significantly reduced, which is consistent with our expectations and the results of previous studies [28]. It also suggests that both of them may participate in the onset and development of HDMEC injury.…”

XIST sponges miR-320d to promote chordoma progression by regulating ARF6

“…Previous studies have indicated that miR-320d served as a tumor suppression miRNA in some cancers, and its downregulation is closely related to the poor prognosis of patients [30] , [31] . In chordoma, miR-320d was lowly expressed, and miR-320d inhibition increased the growth, invasion, and migration of chordoma cells [20] . Consistently, we also uncovered that miR-320d content was declined in chordoma tissues.…”

“…Dysregulated miRNAs are strongly linked with the development of many diseases, including chordoma [17] . Accumulating evidence has revealed that miR-320d has an anti-tumor role in some tumors, including chordoma [18] , [19] , [20] . ADP-ribosylation factor 6 (ARF6) is widely expressed in mammalian cells and is used as a tumor-promoting gene in chordoma [21] .…”

Exosomal miR-320e as a Novel Potential Biomarker for Cerebral Small Vessel Disease

“… 47 Additionally, miR-320 directly targets multiple genes involved in the pathological mechanism of WMH, including Aquaporin-4 (AQP4), E2F transcription factor 1 (E2F1), neuropilin-1 (NrP1), etc. 33 , 48 , 49 Among them, AQP4 contributes to interstitial fluid clearance and lymphatic homeostasis, which is a key protein in several demyelinating diseases. 50 As a cell cycle-related protein, E2F1 is important in neurogenesis and myelination, which has been shown to mediate the promoting effect of overexpressed p53 on oligodendrocyte apoptosis and white matter demyelination in a mouse model of spinal cord compression injury.…”