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

IF 2.2 4区 医学 Q3 ONCOLOGY Cancer Biomarkers Pub Date : 2024-01-01 DOI:10.3233/CBM-230143
Peina He, Zhi Liu, Jinxu Qi, Junrao Shan, Jianyun Sheng
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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.

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长非编码 RNA LINC00885 通过海绵状 miR-654-3p 上调 NCK1 以促进三阴性乳腺癌细胞的活力和迁移。
背景:LINC00885是一种新型致癌长非编码RNA(LncRNA),在多种癌症中上调,但其在三阴性乳腺癌(TNBC)中的功能仍然未知:本研究旨在确定LINC00885对TNBC发展的作用:方法:利用在线数据库确定临床相关性和生存分析。采用 CCK-8 和 Transwell 试验检测 TNBC 细胞株的增殖和迁移行为。通过 RNA pull down 试验检测基因间的相互作用:结果:与正常乳腺癌相比,LncRNA LINC00885在TNBC中高表达。与LINC00885高表达的TNBC患者相比,LINC00885低表达的TNBC患者预后良好。LINC00885的下调抑制了TNBC细胞株的增殖和迁移能力,而LINC00885的高表达则促进了其增殖和迁移能力。在TNBC细胞系中,酪氨酸激酶1的非催化区(NCK1)表达与LINC00885的表达呈正相关,而shRNA介导的NCK1去除了LINC00885上调介导的促瘤效应。结合在线数据库,筛选出miR-654-3p是LINC00885的直接靶基因,它能直接与NCK1的3'-非翻译区(3'-UTR)结合,导致NCK1在TNBC细胞系中的表达下降。LINC00885过表达介导的NCK1上调被miR-654-3p模拟物所抑制。miR-654-3p模拟物能显著缓解LINC00885过表达引起的肿瘤促进作用。然而,在LINC00885缺失表达的细胞中,外源NCK1明显消除了miR-654-3p模拟物的抗肿瘤作用:结论:LINC00885在TNBC中高水平表达。LINC00885通过调节miR-654-3p/NCK1轴促进TNBC细胞株的增殖和迁移。LINC00885有可能成为TNBC的潜在治疗靶点。
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来源期刊
Cancer Biomarkers
Cancer Biomarkers ONCOLOGY-
CiteScore
5.20
自引率
3.20%
发文量
195
审稿时长
3 months
期刊介绍: Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion. The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.
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