Profiling and integrated analysis of differentially expressed circRNAs as novel biomarkers for breast cancer

Abstract

Breast cancer (BC) is a globally common cancer with the highest and increasing morbidity and mortality among females. Novel biomarkers are warranted to be discovered for the early detection, treatment, and prognosis of BC. In this study, we investigated the profiles of differentially expressed (DE) circular RNAs (circRNAs) by competing endogenous RNAs (ceRNA) microarray to construct a genome‐wide circRNA profile. Then, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis of the host genes (HGs) of circRNAs. A total of 4,370 DE circRNAs were detected and GO and KEGG analysis showed that they were significantly associated with cell cycle, DNA replication, BC, and familial BC. We validated the differential circRNAs and relevant HGs through quantitative real‐time polymerase chain reaction and constructed a putative circRNA–microRNA–messenger RNA regulatory network. Eight circRNAs, including hsa_circ_0069094, hsa_circ_0062558, hsa_circ_0074026, hsa_circ_0079876, hsa_circ_0017536, hsa_circ_0023302, hsa_circ_0017650, and hsa_circ_0017545, were validated significantly DE in BC tissue and associated with TNM staging, lymph node infiltration, and Ki67. Hsa_circ_0069094, hsa_circ_0079876, hsa_circ_0017650, and hsa_circ_0017526 were upregulated in plasma. This study revealed the general expression characteristics of specific DE circRNAs in BC and hsa_circ_0069094, hsa_circ_0079876, hsa_circ_0017650, and hsa_circ_0017526 might be promising candidate targets.

Profiling of specific long non‐coding RNA signatures identifies ST8SIA6‐AS1 AS a novel target for breast cancer

“…This may be attributed to the presence of non‐tumor cells in the breast cancer tissues or the secretion of lncRNAs by the breast cancer cells. This type of expression profiling was also observed in our previous work 6 . However, further studies are needed to clarify this phenomenon.…”

“…The probes of competing endogenous RNA microarrays have been used to detect a large number of transcripts in six pairs of breast cancers and adjacent paracancerous normal tissues. The characteristics of cohort 1 were reported in our previous research 6 . The heatmap, scatter plots and volcano plots of differential lncRNAs in breast cancer tissues and paracancerous normal tissues are shown in Figure 1A–1C.…”

“…Total RNA was quantified using a NanoDrop‐2000 spectrophotometer (Thermo Fisher, Watham, MA, USA) and was assessed using a 2100 Bioanalyzer instrument (Agilent Technologies Inc., Santa Clara, CA, USA) to inspect RNA integration. Six pairs of breast cancer and paracancerous tissues were used for microarray analysis to investigate the DE lncRNAs between cancer tissues and paracancerous tissues 6 . The SBC competing endogenous RNA microarray covers 68,423 lncRNAs and 18,853 mRNAs 7 .…”

“…Six pairs of breast cancer and paracancerous tissues were used for microarray analysis to investigate the DE lncRNAs between cancer tissues and paracancerous tissues. 6 The SBC competing endogenous RNA microarray covers 68,423 lncRNAs and 18,853 mRNAs. 7 Total RNA was amplified and labeled prior to purification.…”

“…The characteristics of cohort 1 were reported in our previous research. 6 The heatmap, scatter plots and volcano plots of differential lncRNAs in breast cancer tissues and paracancerous normal tissues are shown in Figure 1A-1C. Figure 1D).…”