长链非编码 RNA LINC00885 通过海绵吸附 miR-654-3p 上调 NCK1 促进三阴性乳腺癌细胞的活力和迁移。

Long noncoding RNA LINC00885 upregulates NCK1 to promote cell viability and migration of triple-negative breast cancer cells through sponging miR-654-3p.

机构信息

Department of Medicine, Pingdingshan University, Pingdingshan, Henan, China.

Department of Gynecotokology, The First People's Hospital of Pingdingshan, Pingdingshan, Henan, China.

出版信息

Cancer Biomark. 2024;39(1):63-78. doi: 10.3233/CBM-230143.

DOI:10.3233/CBM-230143

PMID:37694355

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10977424/

Abstract

BACKGROUND

LINC00885 is a novel oncogenic long noncoding RNA (LncRNA) which is upregulated in various types of cancer, but its function in triple-negative breast cancer (TNBC) remains unknown.

OBJECTIVE

This study aimed to determine the role of LINC00885 on TNBC development.

METHODS

Clinical interrelation and survival analysis were determined using online database. The CCK-8 and Transwell assays were used to detect the proliferation and migration behaviors in TNBC cell lines. The interaction among genes was detected by RNA pull down assay.

RESULTS

LncRNA LINC00885 was highly expressed in TNBC compared to normal breast like. Low levels of LINC00885 was related to good prognosis in TNBC patients compared to TNBC patients with high LINC00885. LINC00885-downregulation inhibited, whereas LINC00885-overexpression promoted the proliferation and migration capability of TNBC cell lines. In TNBC cell lines, noncatalytic region of tyrosine kinase 1 (NCK1) expression was positively associated with LINC00885 expression, and shRNA-mediated the depletion of NCK1 significantly abolished LINC00885 upregulation-mediated pro-tumor effects. Combined with online databases, miR-654-3p was screened as the direct target gene of LINC00885, which could directly bind to 3'-untranslated regions (3'-UTR) of NCK1, resulting in the decreased expression of NCK1 in TNBC cell lines. LINC00885 overexpression-mediated the upregulation of NCK1 was abrogated by miR-654-3p mimics. MiR-654-3p mimics significantly rescued the tumor promotive role caused by LINC00885-overexpression. However, exogenous NCK1 notably eliminated the anti-tumor effects caused by miR-654-3p mimics in LINC00885-overexpressed cells.

CONCLUSIONS

LINC00885 is expressed at a high level in TNBC. LINC00885 promoted proliferation and migration by regulating the miR-654-3p/NCK1 axis in TNBC cell lines. Possibly, LINC00885 can be served as a potential therapeutic target for TNBC.

摘要

背景

LINC00885 是一种新型致癌长链非编码 RNA（LncRNA），在多种类型的癌症中上调，但在三阴性乳腺癌（TNBC）中的作用尚不清楚。

目的

本研究旨在确定 LINC00885 对 TNBC 发展的作用。

方法

使用在线数据库进行临床关联和生存分析。CCK-8 和 Transwell 测定法用于检测 TNBC 细胞系中的增殖和迁移行为。通过 RNA 下拉测定检测基因之间的相互作用。

结果

与正常乳腺相比，LncRNA LINC00885 在 TNBC 中高表达。与 LINC00885 高表达的 TNBC 患者相比，LINC00885 低水平与 TNBC 患者的良好预后相关。LINC00885 下调抑制，而 LINC00885 过表达促进 TNBC 细胞系的增殖和迁移能力。在 TNBC 细胞系中，酪氨酸激酶 1（NCK1）的非催化区域表达与 LINC00885 表达呈正相关，并且 shRNA 介导的 NCK1 耗竭显着消除了 LINC00885 上调介导的促肿瘤作用。结合在线数据库，筛选出 miR-654-3p 作为 LINC00885 的直接靶基因，可直接结合 NCK1 的 3'-非翻译区（3'-UTR），导致 TNBC 细胞系中 NCK1 的表达降低。LINC00885 过表达介导的 NCK1 上调被 miR-654-3p 模拟物阻断。miR-654-3p 模拟物显着挽救了由 LINC00885 过表达引起的肿瘤促进作用。然而，外源性 NCK1 明显消除了 miR-654-3p 模拟物在 LINC00885 过表达细胞中引起的抗肿瘤作用。