长链非编码 RNA HAGLROS 在三阴性乳腺癌中的临床意义及机制。
Clinical significance and mechanism of long noncoding RNA HAGLROS in triple negative breast cancer.
机构信息
Laboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and Technology, Chenggong Campus, 727 South Jingming Road, Kunming, Yunnan 650500, China; Department of Laboratory, Jiangyou People's Hospital, Jiangyou, Sichuan 621700, China.
Laboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and Technology, Chenggong Campus, 727 South Jingming Road, Kunming, Yunnan 650500, China.
出版信息
Pathol Res Pract. 2022 Mar;231:153810. doi: 10.1016/j.prp.2022.153810. Epub 2022 Feb 12.
PURPOSE
Triple Negative Breast Cancer (TNBC) is the malignant tumor with the fastest progression rate in breast cancer. LncRNAs are widely involved in various biological characteristics of tumor. The purpose of this study was to mine LncRNAs that can be used to diagnose and evaluate the prognosis of TNBC.
METHODS
Base on TCGA dataset, we used three R language packages to analyze the differentially expressed (DE) lncRNAs in TNBC. Survival analysis and ROC curve analysis were conducted to estimate the potential diagnostic and prognostic value of LncRNAs for TNBC. Furthermore, CCK-8 and Transwell assays were used to assess the effects of LncRNA on MDA-MB-231 cells proliferation and migration. Additionally, targets mRNAs of candidate LncRNA were predicted by co-expression analysis and multiple target gene prediction databases, then KEGG pathway and GO analysis were conducted using DAVID online tool.
RESULTS
6165 DERNAs and 1258 DElncRNAs were obtained. 40 LncRNAs were significantly correlated with the survival time of TNBC patients. Among them, HAGLROS has the highest HR value. ROC curve analysis also showed that HAGLROS had high sensitivity and specificity. Further in vitro experiments showed that downregulation of HAGLROS inhibited the proliferation and migration of MDA-MB-231 cells. Moreover, by conducting bioinformatics analysis, we found that these target genes of HAGLROS were involved in regulating five signaling pathways. Mechanistic investigations demonstrated that HAGLROS might regulate the expression of PAX5 through miR-330-5p, the effects of miR-330-5p in MDA-MB-231 cells were also analyzed.
CONCLUSION
Our results showed that HAGLROS was significantly overexpressed in TNBC, and high HAGLROS expression predicted poor overall survival. Downregulation of HAGLROS could inhibite the proliferation and migration of MDA-MB-231 cell by regulating PAX5 expression through miR-330-5p.
目的
三阴性乳腺癌（TNBC）是乳腺癌中进展最快的恶性肿瘤。LncRNAs 广泛参与肿瘤的各种生物学特性。本研究旨在挖掘可用于诊断和评估 TNBC 预后的 LncRNAs。
方法
基于 TCGA 数据集，我们使用三个 R 语言包分析 TNBC 中差异表达的（DE）lncRNAs。进行生存分析和 ROC 曲线分析，以评估 LncRNAs 对 TNBC 的潜在诊断和预后价值。此外，使用 CCK-8 和 Transwell 测定法评估 LncRNA 对 MDA-MB-231 细胞增殖和迁移的影响。此外，通过共表达分析和多个靶基因预测数据库预测候选 LncRNA 的靶 mRNAs，然后使用 DAVID 在线工具进行 KEGG 通路和 GO 分析。
结果
获得了 6165 个 DERNAs 和 1258 个 DElncRNAs。有 40 个 LncRNAs 与 TNBC 患者的生存时间显着相关。其中，HAGLROS 的 HR 值最高。ROC 曲线分析也表明 HAGLROS 具有较高的灵敏度和特异性。进一步的体外实验表明，下调 HAGLROS 抑制了 MDA-MB-231 细胞的增殖和迁移。此外，通过进行生物信息学分析，我们发现 HAGLROS 的这些靶基因参与调节五个信号通路。机制研究表明，HAGLROS 可能通过 miR-330-5p 调节 PAX5 的表达，还分析了 miR-330-5p 在 MDA-MB-231 细胞中的作用。
结论
我们的研究结果表明，HAGLROS 在 TNBC 中明显过表达，高 HAGLROS 表达预测总体生存率差。下调 HAGLROS 通过 miR-330-5p 调节 PAX5 的表达可以抑制 MDA-MB-231 细胞的增殖和迁移。
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