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长链非编码 RNA LINC00472 通过与 YBX1 结合调节细胞硬度并抑制肺腺癌的迁移和侵袭。

LncRNA LINC00472 regulates cell stiffness and inhibits the migration and invasion of lung adenocarcinoma by binding to YBX1.

机构信息

Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.

NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.

出版信息

Cell Death Dis. 2020 Nov 3;11(11):945. doi: 10.1038/s41419-020-03147-9.

Abstract

There is increasing evidence that long non-coding RNAs (lncRNAs) play important roles in human tumorigenesis. By using publicly available expression profiling data from lung adenocarcinoma and integrating bioinformatics analysis, we screened a lncRNA, LINC00472. LINC00472 expression in lung adenocarcinoma tissues was significantly lower and tightly associated with patient prognosis and TNM clinical stages in lung adenocarcinoma. LINC00472 also inhibited lung adenocarcinoma cell migration and invasion and increased cell stiffness and adhesion. RNA pull down and RIP assays identified that LINC00472 interacted with the transcription factor Y-box binding protein 1 (YBX1), which partially reversed the inhibition of cell migration and invasion and increased LINC00472-induced cell stiffness and adhesion. LINC00472 also regulated the density and integrity of F-actin in A549 and PC-9 cells possibly via YBX1. LINC00472 inhibited the cell epithelial-mesenchymal transition (EMT) processes via the modulation of YBX1. These results indicated that LINC00472 inhibited the cell EMT process by binding to YBX1, and affected the mechanical properties of the cell, ultimately inhibited its ability to invade and metastasize. Collectively, the present study provides the first evidence that LINC00472 changes the mechanical properties and inhibits the invasion and metastasis of lung adenocarcinoma cells.

摘要

越来越多的证据表明,长非编码 RNA(lncRNA)在人类肿瘤发生中发挥重要作用。通过使用来自肺腺癌的公开可用的表达谱数据,并整合生物信息学分析,我们筛选了一个 lncRNA,LINC00472。肺腺癌组织中的 LINC00472 表达明显降低,与肺腺癌患者的预后和 TNM 临床分期密切相关。LINC00472 还抑制肺腺癌细胞的迁移和侵袭,并增加细胞的刚性和黏附性。RNA 下拉和 RIP 测定鉴定出 LINC00472 与转录因子 Y 盒结合蛋白 1(YBX1)相互作用,这部分逆转了细胞迁移和侵袭的抑制作用,并增加了 LINC00472 诱导的细胞刚性和黏附性。LINC00472 还可能通过 YBX1 调节 A549 和 PC-9 细胞中 F-肌动蛋白的密度和完整性。LINC00472 通过调节 YBX1 抑制细胞上皮-间充质转化(EMT)过程。这些结果表明,LINC00472 通过与 YBX1 结合抑制细胞 EMT 过程,并影响细胞的力学特性,最终抑制其侵袭和转移能力。总之,本研究首次提供证据表明,LINC00472 改变了肺腺癌细胞的力学特性,并抑制了其侵袭和转移。

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