在斑马鱼异种移植物中,长非编码RNA PVT1通过miR-24-3p/NRP1轴预测预后不良并促进结直肠癌癌症的进展。

IF 2 4区 医学 Q3 ONCOLOGY Neoplasma Pub Date : 2023-08-01 DOI:10.4149/neo_2023_221208N1169
Hailin Yin, Shanye Gu, Guiqin Li, Hanxu Yu, Xishan Zhang, Yangsong Zuo
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引用次数: 0

摘要

长链非编码RNA(lncRNA)在人类癌症的发展中起着重要作用。据报道,lncRNA浆细胞瘤变体易位1(PVT1)与癌症(CRC)有关,但其潜在机制仍有待深入探讨,尤其是通过体内模型。在本研究中,生物信息学分析表明,PVT1在CRC组织中的表达水平上调,与CRC患者的不良预后高度相关。在培养的CRC细胞中,敲低PVT1抑制CRC细胞的细胞增殖和迁移,而过表达PVT1促进CRC细胞的进展。在斑马鱼异种移植物中,PVT1的沉默也抑制了CRC细胞的生长和转移。在机制研究中,首先通过starBase预测了PVT1、miR-24-3p和Neuropilin 1(NRP1)之间的结合关系。萤光素酶报告基因分析证实PVT1和NRP1可以直接与miR-24-3p结合。进一步的研究表明,miR-24-3p对CRC细胞的进展具有负调控作用,当敲低PVT1时,miR-24-3 p的抑制作用抵消了CRC进展的抑制作用。此外,NRP1的表达受PVT1的调节,当在体外和体内敲低PVT1时,NRP1过表达可以部分挽救CRC进展的抑制作用。我们的研究表明,PVT1通过调节miR-24-3p/NRP1轴促进CRC的增殖和转移,这为CRC患者提供了预后生物标志物和潜在的治疗靶点。
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Long noncoding RNA PVT1 predicts poor prognosis and promotes the progression of colorectal cancer through the miR-24-3p/NRP1 axis in zebrafish xenografts.

Long noncoding RNAs (lncRNAs) play important roles in the progression of human cancer. It is reported that lncRNA plasmacytoma variant translocation 1 (PVT1) is involved in colorectal cancer (CRC), however, the underlying mechanism remains to be explored deeply, especially by in vivo models. In the present study, bioinformatics analysis showed that the expression level of PVT1 was upregulated in CRC tissues and highly associated with poor prognosis of CRC patients. In cultured CRC cells, knockdown of PVT1 inhibited cell proliferation and migration of CRC cells, while overexpression of PVT1 promoted the progression of CRC cells. In zebrafish xenografts, the silencing of PVT1 also suppressed the growth and metastasis of CRC cells. For mechanism studies, the binding relationships among PVT1, miR-24-3p, and Neuropilin 1 (NRP1) were predicted by starBase firstly. The luciferase reporter assays verified that PVT1 and NRP1 could bind with miR-24-3p directly. Further studies showed miR-24-3p negatively regulated the progression of CRC cells, the inhibition of miR-24-3p counteracted the repression effects of CRC progression when knocking down PVT1. In addition, the expression of NRP1 was regulated by PVT1, and NRP1 overexpression could partially rescue the inhibition effects of CRC progression when knocking down PVT1 in vitro and in vivo. Our study reveals that PVT1 promotes the proliferation and metastasis of CRC via regulating the miR-24-3p/NRP1 axis, which provides a prognosis biomarker and a potential therapeutic target for CRC patients.

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来源期刊
Neoplasma
Neoplasma 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
238
审稿时长
3 months
期刊介绍: The journal Neoplasma publishes articles on experimental and clinical oncology and cancer epidemiology.
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