{"title":"长链非编码RNA LINC01569通过海绵化miR-300上调丝蛋白a相互作用蛋白1-like，阻止三阴性乳腺癌转移。","authors":"Xinyu Jiang, Juli Lin, Zhanlin Zhu","doi":"10.3233/CBM-230261","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Long-chain noncoding RNA (lncRNA), LINC01569, is important for regulating the extracellular matrix, which affects cell migration. However, its involvement in the occurrence and development of triple-negative breast cancer (TNBC) remains unclear.</p><p><strong>Objective: </strong>This study is aimed to investigate the role of LINC01569 on TNBC.</p><p><strong>Methods: </strong>Online database was used for clinical data analysis. Cell viability and migration capability were monitored using cell counting kit-8 and transwell assays, respectively. Luciferase reporter assay and RNA pull-down were used to confirm the binding capability between noncoding RNAs and filamin A-interacting protein 1-like (FILIP1L). Western blotting was used to determine the protein content.</p><p><strong>Results: </strong>Compared with normal breast tissue, LINC01569 was significantly reduced in patients with TNBC subtype, and LINC01569 expression gradually decreased with the progression of tumor stage. Patients with TNBC with high lncRNA LINC01569 levels had a better prognosis than did patients with low LINC01569 levels. LINC01569 overexpression inhibited the migration capability, whereas siRNA-mediated LINC01569 downregulation promoted the migration capability in TNBC cells. Using ENCORI and lncRNA SNP online databases, miR-300 was screened as the potential sponge of LINC01569. The binding of LINC01569 to miR-300 was confirmed using the dual-luciferase reporter and RNA pull-down assays. miR-300 was negatively correlated with LINC01569, and miR-300 mimics eliminated the anti-proliferation and anti-migration effects of LINC01569 on TNBC cells. Additionally, FILIP1L was further verified as the downstream target of miR-300. miR-300 mimics blocked LINC01569 upregulation-mediated elevation of FILIP1L. Importantly, the anti-tumor effects mediated by LINC01569 overexpression were abolished by miR-300 mimics and further restored by FILIP1L upregulation.</p><p><strong>Conclusions: </strong>LINC01569 was expressed at a low level in TNBC and could sponge miR-300 to promote FILIP1L expression, reducing the proliferation and metastasis capability of TNBC. Thus, LINC01569 might be a useful biomarker in the diagnosis and prognosis of metastatic TNBC.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11002719/pdf/","citationCount":"0","resultStr":"{\"title\":\"Long-chain noncoding RNA LINC01569 upregulates filamin A-interacting protein 1-like to prevent metastasis of triple-negative breast cancer via sponging miR-300.\",\"authors\":\"Xinyu Jiang, Juli Lin, Zhanlin Zhu\",\"doi\":\"10.3233/CBM-230261\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Long-chain noncoding RNA (lncRNA), LINC01569, is important for regulating the extracellular matrix, which affects cell migration. However, its involvement in the occurrence and development of triple-negative breast cancer (TNBC) remains unclear.</p><p><strong>Objective: </strong>This study is aimed to investigate the role of LINC01569 on TNBC.</p><p><strong>Methods: </strong>Online database was used for clinical data analysis. Cell viability and migration capability were monitored using cell counting kit-8 and transwell assays, respectively. Luciferase reporter assay and RNA pull-down were used to confirm the binding capability between noncoding RNAs and filamin A-interacting protein 1-like (FILIP1L). Western blotting was used to determine the protein content.</p><p><strong>Results: </strong>Compared with normal breast tissue, LINC01569 was significantly reduced in patients with TNBC subtype, and LINC01569 expression gradually decreased with the progression of tumor stage. Patients with TNBC with high lncRNA LINC01569 levels had a better prognosis than did patients with low LINC01569 levels. LINC01569 overexpression inhibited the migration capability, whereas siRNA-mediated LINC01569 downregulation promoted the migration capability in TNBC cells. Using ENCORI and lncRNA SNP online databases, miR-300 was screened as the potential sponge of LINC01569. The binding of LINC01569 to miR-300 was confirmed using the dual-luciferase reporter and RNA pull-down assays. miR-300 was negatively correlated with LINC01569, and miR-300 mimics eliminated the anti-proliferation and anti-migration effects of LINC01569 on TNBC cells. Additionally, FILIP1L was further verified as the downstream target of miR-300. miR-300 mimics blocked LINC01569 upregulation-mediated elevation of FILIP1L. Importantly, the anti-tumor effects mediated by LINC01569 overexpression were abolished by miR-300 mimics and further restored by FILIP1L upregulation.</p><p><strong>Conclusions: </strong>LINC01569 was expressed at a low level in TNBC and could sponge miR-300 to promote FILIP1L expression, reducing the proliferation and metastasis capability of TNBC. Thus, LINC01569 might be a useful biomarker in the diagnosis and prognosis of metastatic TNBC.</p>\",\"PeriodicalId\":2,\"journal\":{\"name\":\"ACS Applied Bio Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11002719/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Bio Materials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3233/CBM-230261\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3233/CBM-230261","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
摘要
背景:长链非编码RNA (lncRNA)， LINC01569，在调节细胞外基质中起重要作用，影响细胞迁移。然而，它在三阴性乳腺癌(TNBC)发生和发展中的作用尚不清楚。目的:本研究旨在探讨LINC01569在TNBC中的作用。方法:采用在线数据库对临床资料进行分析。分别用细胞计数试剂盒-8和transwell法监测细胞活力和迁移能力。荧光素酶报告基因实验和RNA下拉实验证实了非编码RNA与丝素a相互作用蛋白1样蛋白(filamin A-interacting protein 1-like, FILIP1L)的结合能力。Western blotting法测定蛋白质含量。结果:与正常乳腺组织相比，TNBC亚型患者中LINC01569表达明显降低，且随着肿瘤分期的进展，LINC01569表达逐渐降低。lncRNA LINC01569水平高的TNBC患者预后优于LINC01569水平低的TNBC患者。LINC01569过表达抑制了TNBC细胞的迁移能力，而sirna介导的LINC01569下调则促进了TNBC细胞的迁移能力。利用ENCORI和lncRNA SNP在线数据库，筛选miR-300作为LINC01569的潜在海绵。使用双荧光素酶报告基因和RNA下拉实验证实LINC01569与miR-300的结合。miR-300与LINC01569呈负相关，miR-300模拟物消除了LINC01569对TNBC细胞的抗增殖和抗迁移作用。此外，我们进一步验证了FILIP1L是miR-300的下游靶点。miR-300模拟物阻断了LINC01569上调介导的FILIP1L的升高。重要的是，LINC01569过表达介导的抗肿瘤作用被miR-300模拟物消除，并通过FILIP1L上调进一步恢复。结论:LINC01569在TNBC中低水平表达，可海绵miR-300促进FILIP1L表达，降低TNBC的增殖和转移能力。因此，LINC01569可能是一种有用的生物标志物，用于转移性TNBC的诊断和预后。
Long-chain noncoding RNA LINC01569 upregulates filamin A-interacting protein 1-like to prevent metastasis of triple-negative breast cancer via sponging miR-300.
Background: Long-chain noncoding RNA (lncRNA), LINC01569, is important for regulating the extracellular matrix, which affects cell migration. However, its involvement in the occurrence and development of triple-negative breast cancer (TNBC) remains unclear.
Objective: This study is aimed to investigate the role of LINC01569 on TNBC.
Methods: Online database was used for clinical data analysis. Cell viability and migration capability were monitored using cell counting kit-8 and transwell assays, respectively. Luciferase reporter assay and RNA pull-down were used to confirm the binding capability between noncoding RNAs and filamin A-interacting protein 1-like (FILIP1L). Western blotting was used to determine the protein content.
Results: Compared with normal breast tissue, LINC01569 was significantly reduced in patients with TNBC subtype, and LINC01569 expression gradually decreased with the progression of tumor stage. Patients with TNBC with high lncRNA LINC01569 levels had a better prognosis than did patients with low LINC01569 levels. LINC01569 overexpression inhibited the migration capability, whereas siRNA-mediated LINC01569 downregulation promoted the migration capability in TNBC cells. Using ENCORI and lncRNA SNP online databases, miR-300 was screened as the potential sponge of LINC01569. The binding of LINC01569 to miR-300 was confirmed using the dual-luciferase reporter and RNA pull-down assays. miR-300 was negatively correlated with LINC01569, and miR-300 mimics eliminated the anti-proliferation and anti-migration effects of LINC01569 on TNBC cells. Additionally, FILIP1L was further verified as the downstream target of miR-300. miR-300 mimics blocked LINC01569 upregulation-mediated elevation of FILIP1L. Importantly, the anti-tumor effects mediated by LINC01569 overexpression were abolished by miR-300 mimics and further restored by FILIP1L upregulation.
Conclusions: LINC01569 was expressed at a low level in TNBC and could sponge miR-300 to promote FILIP1L expression, reducing the proliferation and metastasis capability of TNBC. Thus, LINC01569 might be a useful biomarker in the diagnosis and prognosis of metastatic TNBC.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
