circPVT1通过miR-24-3p/let-7a-5p/FSCN1轴促进鼻咽癌细胞侵袭迁移

circPVT1 Promotes Invasion and Migration of Nasopharyngeal Carcinoma Cells Through The miR-24-3p/let-7a-5p/FSCN1 Axis

目的鼻咽癌是一种来源于鼻咽上皮的恶性肿瘤,其临床特征之一是易发生淋巴转移,但是目前鼻咽癌转移的分子机制尚未阐明。circPVT1是由PVT1基因2号外显子反向拼接形成的环状RNA(circRNA),在多种肿瘤中表达上调,本文探讨了circPVT1在鼻咽癌侵袭迁移中的作用和分子机制。方法通过RT-qPCR检测circPVT1及其下游miRNA和FSCN1在鼻咽癌细胞的表达情况,Transwell和划痕愈合实验检测circPVT1对鼻咽癌细胞侵袭迁移的影响,RNA pull-down实验检测circPVT1结合的miRNA,双荧光素酶报告实验检测miR-24-3p和let-7a-5p靶向抑制FSCN1 mRNA表达。结果在鼻咽癌细胞中过表达circPVT1可以促进鼻咽癌细胞侵袭迁移,而敲低circPVT1则可以抑制鼻咽癌细胞的侵袭迁移。进一步研究发现,circPVT1可以通过竞争性吸附miR-24-3p和let-7a-5p,上调FSCN1的表达,从而促进鼻咽癌细胞的侵袭迁移。结论circPVT1通过miR-24-3p/let-7a-5p/FSCN1轴促进鼻咽癌细胞侵袭迁移,证实circPVT1是鼻咽癌发生发展过程中一个重要驱动因子。

Objective The study aims to explore the role and molecular mechanism of circPVT1 in invasion and migration of nasopharyngeal carcinoma(NPC),a malignant tumor originating from nasopharyngeal epithelium with the clinical feature of lymph node metastasis.circPVT1,a circular RNA formed by back splicing of exon 2 of PVT1 gene,has been found to be upregulated in various tumors and plays an important role in tumorigenesis.The study investigated the role and molecular mechanism of circPVT1 in invasion and migration of NPC cells.Methods We detected the expression of circPVT1 and its downstream miRNAs and FSCN1 in NPC cells using RT-qPCR,and evaluated the effect of circPVT1 on NPC cell invasion and migration using Transwell and scratch healing experiments.RNA pull-down experiment was used to detect the miRNAs bound by circPVT1,and the dual luciferase reporter assay was used to detect the targeting of FSCN1 mRNA by miR-24-3p and let-7a-5p.Results The study found that overexpression of circPVT1 in NPC cells can promote invasion and migration,while knockdown of circPVT1 can inhibit NPC cells invasion and migration.Further studies revealed that circPVT1 upregulates the expression of FSCN1 by competitively adsorbing miR-24-3p and let-7a-5p.Conclusion circPVT1 promotes invasion and migration of NPC cells through the miR-24-3p/let-7a-5p/FSCN1 axis,and is an important driving factor in the development of NPC.