LINC00467, Driven by Copy Number Amplification and DNA Demethylation, Is Associated with Oxidative Lipid Metabolism and Immune Infiltration in Breast Cancer

Abstract

Breast cancer (BRCA) is a malignant tumor with a high incidence and poor prognosis in females. However, its pathogenesis remains unclear. In this study, based on bioinformatic analysis, we found that LINC00467 was highly expressed in BRCA and was associated with tumor metastasis and poor prognosis. The genomic and epigenetic analysis showed that LINC00467 may also be regulated by copy number amplification (CNA), chromatin openness, and DNA methylation. In vitro experiments showed that it could promote the proliferation, migration, and invasion of BRCA cells. Competitive endogenous RNA (ceRNA) regulatory network analysis and weighted gene coexpression network analysis (WGCNA) suggested that LINC00467 may play a role in signaling pathways of peroxisomal lipid metabolism, immunity, and others through microRNAs (miRNAs) targeting transforming growth factor beta 2 (TGFB2). In addition, copy number amplification and high expression of LINC00467 were associated with the low infiltration of CD8+ and CD4+ T cells. In conclusion, we found that LINC00467, driven by copy number amplification and DNA demethylation, may be a potential biomarker for the diagnosis and prognosis of BRCA and a tumor promoter acting as a potential therapeutic target for BRCA as well.

A review on the role of LINC00467 in the carcinogenesis

“…Moreover, LINC00467 could enhance expression of LIN28B through directly interacting with it [6]. Another in silico study in breast cancer has shown possible role of LINC00467 in the regulation of peroxisomal lipid metabolism and immune response through targeting miRNAs [7].…”

“…Genomic and epigenetic analyses have shown the impact of copy number amplification, chromatin configuration, and methylation status of DNA on expression of this lncRNA. Copy number amplification and up-regulation of LINC00467 has been associated with the lower levels CD8 + and CD4 + T cells infiltrations [7]. LINC00467 level has also been reported to be elevated in colorectal cancer tissues compared with normal colon mucosal counterparts.…”

“…Copy number variations within LINC00467 have been associated expression levels of this lncRNA, immune infiltration in lung adenocarcinoma and poor clinical outcome [38]. Moreover, LINC00467 expression in breast cancer has been associated with immune infiltration [7].…”

LINC00467: an oncogenic long noncoding RNA

“…The expression level of LINC00467 in BC tissues and cells is obviously upregulated compared with paired adjacent tissues and normal breast epithelial cells. Functionally, several research revealed that silencing LINC00467 could suppress BC cell proliferation, migration and invasion [42,43]. Mechanically, LINC00467 down-regulated miR-138-5p and protein level of lin-28 homolog B (LIN28B) via a direct interaction to serve as a potential target [43].…”

“…Mechanically, LINC00467 down-regulated miR-138-5p and protein level of lin-28 homolog B (LIN28B) via a direct interaction to serve as a potential target [43]. In addition, Bo et al [42]. explored more mechanisms that high expression of LINC00467 driven by DNA methylation is associated with the protein TGF-β2 expression and LINC00467 correlated with the infiltration of CD4 + and CD8 + T cells suggests that LINC00467 was likely to inhibit anti-tumor immunity.…”