长链非编码RNA DLG1-AS1通过下调miR-203促进三阴性乳腺癌细胞增殖。
LncRNA DLG1-AS1 Promotes Cancer Cell Proliferation in Triple Negative Breast Cancer by Downregulating miR-203.
作者信息
Li Shuyan
机构信息
Department of Breast Surgery, Yantai Mountain Hospital, Yantai, P.R. China.
出版信息
J Breast Cancer. 2020 Aug;23(4):343-354. doi: 10.4048/jbc.2020.23.e46.
PURPOSE
The oncogenic role of long non-coding RNA (lncRNA) DLG1-AS1 has been studied in cervical cancer, but its involvement in triple negative breast cancer (TNBC) is unknown. Here, we aimed to investigate the possible role and underlying mechanism of DLG1-AS1 in TNBC.
METHODS
The differential expression of DLG1-AS1 and miR-203 in TNBC tissues and cells was determined using quantitative polymerase chain reaction assays. Correlations between DLG1-AS1 and miR-203 expression across TNBC tissues and non-tumor tissues were analyzed using Spearman rank correlation test. The effects of DLG1-AS1 and miR-203 overexpression, and DLG1-AS1 knockdown on the metastasis of BT-549 and MDA-MB-157 cells were evaluated using a transwell assay. The effects of DLG1-AS1 and miR-203 overexpression on the proliferation of BT-549 and MDA-MB-157 cells were evaluated using Cell Counting Kit-8 and cell colony formation assays.
RESULTS
We found that DLG1-AS1 was upregulated whereas miR-203 was downregulated in tumor tissues of patients and in TNBC cells compared to the adjacent healthy tissues of patients with TNBC and in normal breast MCF-10A cells, respectively. Further, DLG1-AS1 and miR-203 were inversely correlated in tumor tissues. DLG1-AS1 overexpression mediated downregulation of miR-203, whereas miR-203 overexpression had no significant effects on DLG1-AS1 expression. DLG1-AS1 expression was increased, whereas miR-203 levels were decreased with advancing clinical stages. TNBC cell migration was promoted by DLG1-AS1 overexpression and inhibited by miR-203 overexpression or DLG1-AS1 knockdown. Moreover, TNBC cell proliferation was promoted by DLG1-AS1 overexpression and inhibited by miR-203 overexpression. Further, miR-203 overexpression reduced the effects of DLG1-AS1 overexpression.
CONCLUSION
These results indicate that DLG1-AS1 may promote cancer cell proliferation in TNBC by downregulating the tumor suppressor miR-203.
目的
长链非编码RNA（lncRNA）DLG1-AS1在宫颈癌中的致癌作用已得到研究，但其在三阴性乳腺癌（TNBC）中的作用尚不清楚。在此，我们旨在研究DLG1-AS1在TNBC中的可能作用及潜在机制。
方法
采用定量聚合酶链反应检测TNBC组织和细胞中DLG1-AS1和miR-203的差异表达。使用Spearman等级相关检验分析TNBC组织和非肿瘤组织中DLG1-AS1与miR-203表达之间的相关性。采用Transwell实验评估DLG1-AS1和miR-203过表达以及DLG1-AS1敲低对BT-549和MDA-MB-157细胞转移的影响。使用细胞计数试剂盒-8和细胞集落形成实验评估DLG1-AS1和miR-203过表达对BT-549和MDA-MB-157细胞增殖的影响。
结果
我们发现，与TNBC患者的相邻健康组织以及正常乳腺MCF-10A细胞相比，DLG1-AS1在患者肿瘤组织和TNBC细胞中上调，而miR-203分别下调。此外，肿瘤组织中DLG1-AS1与miR-203呈负相关。DLG1-AS1过表达介导miR-203下调，而miR-203过表达对DLG1-AS1表达无显著影响。随着临床分期进展，DLG1-AS1表达增加，而miR-203水平降低。DLG1-AS1过表达促进TNBC细胞迁移，miR-203过表达或DLG1-AS1敲低则抑制细胞迁移。此外，DLG1-AS1过表达促进TNBC细胞增殖，miR-203过表达则抑制细胞增殖。进一步研究发现，miR-203过表达可降低DLG1-AS1过表达的作用。
结论
这些结果表明DLG-AS1可能通过下调抑癌基因miR-203促进TNBC癌细胞增殖。
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