长链非编码RNA AC012073.1对乳腺癌细胞迁移侵袭的影响及临床价值

doi:10.6040/j.issn.1671-7554.0.2021.0166

摘要/Abstract

摘要： 目的探讨长链非编码RNA(lncRNA)AC012073.1在乳腺癌中的表达及对细胞迁移侵袭的影响,并对其临床价值进行研究。方法运用高通量芯片和TCGA数据挖掘分析在乳腺癌组织中高表达并与患者预后不良相关的lncRNAs。实时荧光定量PCR(qRT-PCR)检测AC012073.1在乳腺癌细胞和血清中的表达水平。通过小干扰或质粒转染技术敲减或过表达AC012073.1,并采用Transwell和划痕实验检测其对细胞迁移与侵袭能力的影响。TargetScan等数据库对下游作用靶点和功能富集分析进行预测,并运用Cytoscape软件绘制ceRNA调控网络。采用受试者工作曲线(ROC)分析血清AC012073.1对乳腺癌的诊断效能。结果筛选发现一种新型lncRNA AC012073.1,并在乳腺癌组织中高表达(P<0.001),且与患者预后不良关联(P=0.031),乳腺癌细胞系中AC012073.1表达水平均高于正常乳腺上皮细胞,差异具有统计学意义(P<0.05)。MDA-MB-231和MCF-7两株细胞功能实验结果显示,敲减AC012073.1明显抑制细胞迁移和侵袭能力,反之过表达AC012073.1后,细胞的迁移和侵袭能力明显增强。下游靶点和基因通路分析结果显示,AC012073.1可通过调控肿瘤经典信号通路促进乳腺癌的进展。qRT-PCR结果显示,与健康对照相比,乳腺癌患者血清中AC012073.1的表达较高且具有统计学意义(P<0.001),ROC曲线结果显示曲线下面积(AUC)为0.833,表明其对乳腺癌具有良好的诊断价值。结论研究表明AC012073.1在乳腺癌中高表达,促进乳腺癌细胞的迁移和侵袭,并可能成为乳腺癌诊断和预后的生物标志物。

关键词: 长链非编码RNA, 乳腺癌, 迁移, 侵袭, 生物标志物

Abstract: Objective To explore the expression of long non-coding RNA(lncRNA)AC012073.1 and its effects on the migration and invasion of human breast cancer(BC)cells. Methods The lncRNAs which were upregulated in BC tissues and related to poor prognosis were screened with lncRNA microarray and the cancer genome atlas(TCGA). The expression of AC012073.1 in BC cells and serum was detected with quantitative real-time PCR(qRT-PCR). MDA-MB-231 and MCF-7 cells were transfected with AC012073.1 siRNAs or plasmid and the transfection efficiency was detected with qRT-PCR. Cell migration and invasion were then determined with transwell assay and wound healing assay, respectively. The downstream targets and function enrichment analysis were predicted with TargetScan, and a regulatory network of ceRNA was constructed with Cytoscape software. The diagnostic efficacy of serum AC012073.1 for BC was analyzed with receiver operating characteristic(ROC)curve. Results A novel lncRNA, AC012073.1, was identified, which was significantly upregulated in BC tissues(P<0.001)and associated with poor prognosis(P=0.031). Compared with normal breast epithelial cells, BC cell lines had elevated expression of AC012073.1(P<0.05). Knockdown of AC012073.1 significantly inhibited cell migration and invasion, but overexpression of AC012073.1 promoted cell migration and invasion. The downstream targets and gene ontology(GO)analysis indicated that AC012073.1 promoted BC progression by regulating typical tumor signaling pathways. The qRT-PCR results showed the expression of AC012073.1 significantly increased in BC serum samples(P<0.001). The area under ROC curve(AUC)was 0.833, indicating it had a great diagnostic value for BC. Conclusion Highly expressed in BC, AC012073.1 promotes the migration and invasion of BC cells, and may serve as a potential biomarker for the diagnosis and prognosis of BC.

Key words: LncRNA, Breast cancer, Migration, Invasion, Biomarker

中图分类号:

R737.9

孔雪,李娟,段伟丽,史爽,李培龙,杜鲁涛,毛海婷,王传新. 长链非编码RNA AC012073.1对乳腺癌细胞迁移侵袭的影响及临床价值[J]. 山东大学学报 (医学版), 2021, 59(4): 70-78.

KONG Xue, LI Juan, DUAN Weili, SHI Shuang, LI Peilong, DU Lutao, MAO Haiting, WANG Chuanxin. Effects of lncRNA AC012073.1 on the migration and invasion of human breast cancer cells and its clinical significance[J]. Journal of Shandong University (Health Sciences), 2021, 59(4): 70-78.

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