基于综合分析对与乳腺癌骨转移相关的长链非编码RNA的新见解。
New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis.
作者信息
Zhang Yu, Huang Xiaofeng, Liu Jin, Chen Guo, Liu Chengjun, Zhang Sen, Li Jiaxin
机构信息
Department of Orthopaedics, The First People's Hospital of Chengdu, Chengdu, Sichuan Province, China.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, People's Republic of China.
出版信息
Cancer Cell Int. 2021 Jul 13;21(1):372. doi: 10.1186/s12935-021-02068-7.
BACKGROUND
Bone is the most common site of metastatic breast cancer, and it is a leading cause of breast cancer-related death. This study aimed to explore bone metastasis-related long non-coding RNAs (lncRNAs) in breast cancer.
METHODS
Four mRNA datasets and two lncRNA datasets of bone metastasis, lung metastasis and liver metastasis of breast cancer were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, as well as the overlap of the two groups, were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction (PPI) network construction of DEmRNAs were conducted. The cis nearby-targeted DEmRNAs of DElncRNAs were obtained. Quantitative real-time polymerase chain reactions (qRT-PCR) was used to detect the expression levels of selected DEmRNAs and DElncRNAs. LOC641518-lymphoid enhancer-binding factor 1 (LEF1) pair was selected to verify its role in migration and invasion capability of breast cancer cells by wounding healing assay and transwell invasion assay.
RESULTS
A total of 237 DEmRNAs were obtained in bone metastasis compared with both lung metastasis and liver metastasis. A total of three DElncRNAs in bone metastasis compared with both lung metastasis and liver metastasis were obtained. A total of seven DElncRNA-nearby-targeted DEmRNA pairs and 15 DElncRNA-nearby-targeted DEmRNA pairs in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, were detected, respectively. Four cis LncRNA-mRNA interaction pairs were identified, which are LOC641518-LEF1, FLJ35024-Very Low Density Lipoprotein Receptor (VLDLR), LOC285972-Retinoic Acid Receptor Responder 2 (RARRES2) and LOC254896-TNF receptor superfamily member 10c (TNFRSF10C). qRT-PCR using clinical samples from our hospital confirms the bioinformatics prediction. siRNA knocking down LOC641518 down-regulates LEF1 mRNA expression, and reduces the migration and invasion capability of breast cancer cells.
CONCLUSIONS
We concluded that four LncRNA-mRNA pairs, including LOC641518-LEF1, may play a central role in breast cancer bone metastasis.
背景
骨是转移性乳腺癌最常见的部位，也是乳腺癌相关死亡的主要原因。本研究旨在探索乳腺癌中与骨转移相关的长链非编码RNA（lncRNA）。
方法
从基因表达综合数据库（GEO）下载了4个乳腺癌骨转移、肺转移和肝转移的mRNA数据集以及2个lncRNA数据集。确定了骨转移组与肺转移组、骨转移组与肝转移组中差异表达的mRNA（DEmRNA）和lncRNA（DElncRNA），以及两组的重叠部分。对DEmRNA进行了基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析以及蛋白质-蛋白质相互作用（PPI）网络构建。获得了DElncRNA的顺式邻近靶向DEmRNA。采用定量实时聚合酶链反应（qRT-PCR）检测所选DEmRNA和DElncRNA的表达水平。选择LOC641518-淋巴样增强因子结合因子1（LEF1）对，通过划痕愈合试验和Transwell侵袭试验验证其在乳腺癌细胞迁移和侵袭能力中的作用。
结果
与肺转移和肝转移相比，在骨转移中总共获得了237个DEmRNA。与肺转移和肝转移相比，在骨转移中总共获得了3个DElncRNA。在骨转移组与肺转移组、骨转移组与肝转移组中，分别检测到总共7对和15对DElncRNA邻近靶向DEmRNA。鉴定出4对顺式LncRNA-mRNA相互作用对，分别为LOC641518-LEF1、FLJ35024-极低密度脂蛋白受体（VLDLR）、LOC285972-视黄酸受体应答因子2（RARRES2）和LOC254896-TNF受体超家族成员10c（TNFRSF10C）。使用我院临床样本进行的qRT-PCR证实了生物信息学预测。敲低LOC641518的小干扰RNA（siRNA）下调LEF1 mRNA表达，并降低乳腺癌细胞的迁移和侵袭能力。
结论
我们得出结论，包括LOC641518-LEF1在内的4对LncRNA-mRNA对可能在乳腺癌骨转移中起核心作用。
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