Identification of circular RNAs as a promising new class of diagnostic biomarkers for human breast cancer

Abstract

Endogenous noncoding circular RNAs (circRNAs) have gained attention for their involvement in carcinogenesis, but their expression pattern in breast cancer has remained largely unknown. In this two-stage study, we first used an Arraystar Human circRNA Array to construct a genome-wide circRNA profile. We then selected candidate circRNAs for validation using a quantitative real-time polymerase chain reaction system. CircRNA/miRNA interactions were predicted and sequence analyses were performed. Among 1155 differentially expressed circRNAs, 715 were upregulated and 440 were downregulated in breast cancer tissues. The validation study demonstrated that hsa_circ_103110, hsa_circ_104689 and hsa_circ_104821 levels were elevated in breast cancer tissues, whereas hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were downregulated. These circRNAs targeted complementary miRNA response elements. The area under the receiver operating characteristic curve for distinguishing breast cancer was 0.82 (95% CI: 0.73-0.90) when hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were used in combination. This study provides evidence that circRNAs are differentially expressed in breast cancer and are important in carcinogenesis because they participate in cancer-related pathways and sequester miRNAs.

Competing endogenous RNA (ceRNA) cross talk and language in ceRNA regulatory networks: A new look at hallmarks of breast cancer

“…In the recent years, circRNAs have received considerable attention because accumulating evidences indicate that they play important roles in the development and progression of various cancers through functioning as a sponge for miRNAs (Kristensen, Hansen, Venø, & Kjems, 2018;Kulcheski, Christoff, & Margis, 2016;Wang, Xiao, Wu, & Ma, 2018). In the case of BC, several recent reports have demonstrated the key roles of dysregulated circRNAs in the breast tumor development as well as its clinicopathological outputs, thereby show diagnostic and therapeutic biomarker values (Lü et al, 2017; H. Wang, Xiao, et al, 2018).…”

Unearthing Regulatory Axes of Breast Cancer circRNAs Networks to Find Novel Targets and Fathom Pivotal Mechanisms

“…In parallel with functioning as transcription and translation regulator, the ecRNAs act as miRNAs sponges enjoying MREs [9]. The circRNA profile of BC versus normal tissues introduces manifold anti-breast cancer controllable targets [10]. Suppression of circIRAK3 leads to down-regulation of FOXC1 through miR-3607-FOXC1 axes and promotes BC cell metastasis [11].…”

Circular RNA; a new biomarker for breast cancer: A systematic review

“…In the study conducted by Lu et al, among 1,155 differentially expressed circRNAs, a total of 715 circRNAs were notably overexpressed, and 440 were remarkably downregulated in the BC lesions compared with healthy tissue samples. Investigators also demonstrated that hsa_circ_103110, hsa_circ_104689, and hsa_circ_104821 levels were surprisingly elevated in BC tissue samples in contrast with healthy ones; whereas hsa_circ_406697, hsa_circ_100219, and hsa_circ_006054 were significantly downregulated(Lu et al, 2017).…”