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LINC01089 通过靶向 miR-301b-3p/HPDG 轴抑制 YY1 抑制肺癌的进展。

LINC01089, suppressed by YY1, inhibits lung cancer progression by targeting miR-301b-3p/HPDG axis.

机构信息

Department of Thoracic Surgery, The Second Affiliated Hospital of Nanjing Medical University, No.121 Jiangjiayuan Road, Gulou District, Nanjing, Jiangsu, 210011, People's Republic of China.

出版信息

Cell Biol Toxicol. 2022 Dec;38(6):1063-1077. doi: 10.1007/s10565-021-09643-8. Epub 2021 Sep 24.

Abstract

PURPOSE

LINC01089 is a newly identified lncRNA and rarely reported in human cancers. Our study aimed to investigate its role in lung cancer.

METHODS

YY1, LINC01089, and miR-301b-3p levels in lung cancer tissues and cells were assessed using qRT-PCR. Bioinformatics analysis and luciferase reporter, ChIP, and RIP assays were carried out for determining the relationships among YY1, LINC01089, miR-301b-3p, and HPGD. Gain- and loss-of-function assays were carried out to confirm the impacts of LINC01089 and HPDG in lung cancer cells. CCK-8 assay was used to assess cell proliferation rate, and Transwell assay was applied to measure cell invasion and migration. An in vivo tumor model was applied for validating the role of LINC01089.

RESULTS

LINC01089 was decreased in lung cancer tissues and cells, and low LINC01089 level predicted a poor clinical outcome. YY1 directly bound to LINC01089 promoter region and inhibited its transcription. LINC01089 knockdown thwarted the proliferation, invasion, and migration capacity of H1299 and A549 cells and aggravated tumor growth. Specifically, LINC01089 functioned as a competing endogenous RNA of miR-301b-3p to modulate HPGD and thereby affected lung cancer progression.

CONCLUSION

Our data revealed that LINC01089, directly suppressed by YY1, inhibited lung cancer progression by targeting the miR-301b-3p/HPGD axis. Graphical abstract 1. LINC01089 expression was downregulated in lung cancer tisuues and cell lines, and low LINC01089 levels predicted a poor clinical outcome. 2. LINC01089 knockdown enhanced proliferation, invasion, and migration of H1299 and A549 cells in vitro and promoted lung cancer cell tumorigenesis and metastasis in vivo. 3. LINC01089, directly suppressed by YY1, functioned as a competing endogenous RNA against miR-301b-3p to increase HPGD expression.

摘要

目的

LINC01089 是一种新发现的长链非编码 RNA,在人类癌症中鲜有报道。本研究旨在探讨其在肺癌中的作用。

方法

采用 qRT-PCR 检测肺癌组织和细胞中的 YY1、LINC01089 和 miR-301b-3p 水平。通过生物信息学分析、荧光素酶报告基因、染色质免疫沉淀(ChIP)和 RNA 免疫沉淀(RIP)实验确定 YY1、LINC01089、miR-301b-3p 和 HPGD 之间的关系。通过 gain- 和 loss-of-function 实验验证 LINC01089 和 HPGD 在肺癌细胞中的作用。CCK-8 法检测细胞增殖率,Transwell 法检测细胞侵袭和迁移。体内肿瘤模型验证 LINC01089 的作用。

结果

LINC01089 在肺癌组织和细胞中表达下调,低水平的 LINC01089 预示着不良的临床结局。YY1 直接结合 LINC01089 启动子区域并抑制其转录。LINC01089 敲低削弱了 H1299 和 A549 细胞的增殖、侵袭和迁移能力,并加重了肿瘤生长。具体而言,LINC01089 作为 miR-301b-3p 的竞争性内源 RNA 发挥作用,调节 HPGD,从而影响肺癌的进展。

结论

我们的数据表明,LINC01089 被 YY1 直接抑制,通过靶向 miR-301b-3p/HPGD 轴抑制肺癌进展。

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