Comprehensive Analysis of Differentially Expressed Profiles of lncRNAs/mRNAs and miRNAs with Associated ceRNA Networks in Triple-Negative Breast Cancer
Authors:
Open Access
- 11 October 2018
- journal article
- research article
- Published by S. Karger AG in Cellular Physiology and Biochemistry
- Vol. 50 (2) , 473-488
Abstract
Background/Aims: Triple-negative breast cancer (TNBC) is a subtype of highly malignant breast cancer with poor prognosis. Growing evidence indicates that Long noncoding RNAs (lncRNAs) play important regulatory roles in the development and progression of a variety of cancers including breast cancer. However, the underlying mechanisms remain largely unknown. Methods: Here, we compared the expression profiles of mRNAs, lncRNAs and miRNAs between 111 TNBC tissues and 104 non-cancerous tissues utilizing RNA-Seq Data from The Cancer Genome Atlas (TCGA). Gene Ontology and KEGG pathway enrichment analyses were executed to investigate the principal functions of the significantly dysregulated mRNAs. Moreover, Kaplan-Meier survival analyses were performed to determine the effects of differentially expressed lncRNAs/mRNAs/miRNAs on overall survival. Subsequently, we constructed a competing endogenous RNA (ceRNA) network, which included 66 dysregulated lncRNAs, 24 miRNAs and 55 mRNAs. The four dysregulated lncRNAs, three aberrantly expressed miRNAs and four mRNAs were confirmed in the ceRNA network by qRT-PCR in 30 pairs of samples, respectively. Results: A total of 1441 lncRNAs, 114 miRNA and 2501 mRNAs were found to be differentially expressed in TNBC tissues compared with controls. 109 lncRNAs and 124 mRNAs might serve as prognostic signature for patients with TNBC according to the survival analysis. Functional analysis revealed that 19 mRNAs in the ceRNA network were enriched in 17 cancer-related pathways. Conclusion: Taken together, we identified novel lncRNAs/miRNAs which may serve as potential biomarkers to predict the survival and therapeutic targets for TNBC patients based on a large-scale sample. More importantly, we constructed the ceRNA network of TNBC, which provides valuable information to further explore the molecular mechanism underlying tumorigenesis and development of TNBC.Keywords
This publication has 40 references indexed in Scilit:
- MicroRNA-33a and let-7e inhibit human colorectal cancer progression by targeting ST8SIA1The International Journal of Biochemistry & Cell Biology, 2017
- LncRNA MEG3 inhibits cell epithelial-mesenchymal transition by sponging miR-421 targeting E-cadherin in breast cancerBiomedicine & Pharmacotherapy, 2017
- MiR-216a decreases MALAT1 expression, induces G2/M arrest and apoptosis in pancreatic cancer cellsBiochemical and Biophysical Research Communications, 2017
- Long non-coding RNAs: An emerging powerhouse in the battle between life and death of tumor cellsDrug Resistance Updates, 2016
- LINC01225 promotes occurrence and metastasis of hepatocellular carcinoma in an epidermal growth factor receptor-dependent pathwayCell Death & Disease, 2016
- miR‐206 inhibits cell migration through direct targeting of the actin‐binding protein Coronin 1C in triple‐negative breast cancerMolecular Oncology, 2014
- Chk1 as a new therapeutic target in triple-negative breast cancerThe Breast, 2014
- Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1)Cell Death & Disease, 2014
- Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expressionCancer Letters, 2013
- A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?Cell, 2011