Expression profile analysis of long noncoding RNA in HER-2-enriched subtype breast cancer by next-generation sequencing and bioinformatics

Abstract

BackgroundHuman epidermal growth factor receptor 2 (HER-2)-enriched subtype breast cancer is associated with a more aggressive phenotype and shorter survival time. Long non-coding RNAs (LncRNAs) have essential roles in tumorigenesis and occupy a central place in cancer progression. Notably, few studies have focused on the dysregulation of LncRNAs in the HER-2-enriched subtype breast cancer. In this study, we analyzed the expression profile of LncRNAs and mRNAs in this particular subtype of breast cancer.MethodsSeven pairs of HER-2-enriched subtype breast cancer and normal tissue were sequenced. We screened out differently expressed genes and measured the correlation of the expression levels of dysregulated LncRNAs and HER-2 by Pearson’s correlation coefficient analysis. Gene ontology analysis and pathway analysis were used to understand the biological roles of these differently expressed genes. Pathway act network and coexpression network were constructed.ResultsMore than 1,300 LncRNAs and 2,800 mRNAs, which were significantly differently expressed, were identified. Among these LncRNAs, AFAP1-AS1 was the most dysregulated LncRNA, while ORM2 was the most dysregulated mRNA. LOC100288637 had the highest positive correlation coefficient of 0.93 with HER-2, while RPL13P5 had the highest negative correlation coefficient of −0.87. The pathway act network showed that MAPK signaling pathway, PI3K-Akt signaling pathway, metabolic pathways, cell cycle, and regulation of actin cytoskeleton were highly related with HER-2-enriched subtype breast cancer. Coexpression network recognized LINC00636, LINC01405, ADARB2-AS1, ST8SIA6-AS1, LINC00511, and DPP10-AS1 as core genes.ConclusionThese results analyze the functions of LncRNAs and provide useful information for exploring candidate therapeutic targets and new molecular biomarkers for HER-2-enriched subtype breast cancer.

Long Intergenic Noncoding RNA 00511 Acts as an Oncogene in Non–small-cell Lung Cancer by Binding to EZH2 and Suppressing p57

“…The levels of certain lncRNAs are associated with the metastasis, development, and prognosis of cancers. 44,45,46,47,48 Given that LINC00511 is upregulated in breast cancer, 45,46 and silence of LINC00511 showed tumor-suppressive roles via inhibition of cell proliferation in breast cancer. 45 We speculated that LINC00511 might involve in the NSCLC progression.…”

Targeted therapies in breast cancer: New challenges to fight against resistance

“…Compensatory survival pathways, increased phosphatydil-inositol-3-kinase (PI3K)[49-52] signaling, receptor tyrosine kinase signaling outside the ErbB/HER family and involvement of other HER receptors[53], may all play a key role in the development of alternative molecular pathways responsible for the development of therapeutic resistance in breast cancer cells.…”

Endogenous retroviral promoter exaptation in human cancer

“…The Ref-Seq annotated lncRNA AFAP1 antisense RNA 1 ( AFAP1-AS1 ) runs antisense to the actin filament associated protein 1 ( AFAP1 ) gene and several publications report its up-regulation and association with poor survival in a number of solid tumor types [155–158]. While the oncogenic mechanism of AFAP1-AS1 has not been extensively studied, one report presented evidence that it promotes cell proliferation by upregulating RhoA/Rac2 signaling [159] and its expression inversely correlates with AFAP1 .…”