Abstract
BackgroundBone 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.MethodsFour 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.ResultsA 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.ConclusionsWe concluded that four LncRNA-mRNA pairs, including LOC641518-LEF1, may play a central role in breast cancer bone metastasis.
Highlights
Breast cancer is the most common malignancy in women [1]
There is lack of systemic LncRNA-mRNA network analysis based on human database, so it is necessary to explore important long non-coding RNAs (lncRNAs) associated with breast cancer bone metastasis
Identification of differentially expressed mRNAs (DEmRNAs) in tumor tissues from bone metastatic sites compared with other metastatic sites of breast cancer Compared with lung metastatic sites, a total of 1280 DEmRNAs (645 up- and 635 down-regulated mRNAs) were detected in tumor tissues from bone metastatic sites of breast cancer
Summary
Breast cancer is the most common malignancy in women [1]. Gooding et al indicated that the lncRNA BORG drives breast cancer metastasis to lung and disease recurrence [7]. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), previously described as a metastasis-promoting lncRNA, was reported to suppress breast cancer metastasis [8]. HOXA11-AS was demonstrated to promote breast cancer invasion and lymph node metastasis through affecting epithelial-mesenchymal transition [9]. There are few studies on bone metastasis-related lncRNAs in breast cancer. There is lack of systemic LncRNA-mRNA network analysis based on human database, so it is necessary to explore important lncRNAs associated with breast cancer bone metastasis. This study aimed to explore bone metastasis-related long non-coding RNAs (lncRNAs) in breast cancer
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