Circular RNAs (circRNAs) are a type of noncoding RNAs with a closed loop structure. With the development of high-throughput sequencing, massive circRNAs have been discovered in tumorous tissues. Emerging evidence suggests that the biological functions of circRNAs including serving as ceRNAs or miRNA sponges, interacting with proteins, regulating gene transcription and translation, suggesting that circRNAs will be novel biomarkers and targets for the diagnosis and prognosis of diseases. Breast cancer is the most frequently occurring cancer and the leading cause of cancer-related death among women worldwide. It is vital to understand the molecular pathways involved in the pathogenesis of proliferation and progression. In this review, we summarize the current knowledge on human circRNAs and their potential clinical implications on breast cancer.

MicroRNAs are a small class of non-coding RNAs with a critical role in the tumorigenesis and maintenance of breast cancer through binding to the 3'‑untranslated regions of target mRNAs, which causes a block of translation and/or mRNA degradation. The purpose of this study was to investigate the expression of microRNA-497 (miR-497) as well as its potential role in human breast cancer. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to determine the expression pattern of miR-497 in breast cancer and normal breast tissues. Correlation analysis was conducted to characterize the association of miR-497 expression abnormality with pathological factors. Proliferation, cell cycle and apoptosis assays were conducted to explore the potential function of miR-497 in human MCF-7 breast cancer cells. RT-PCR and Western blot analysis were employed to validate the downstream targets of miR-497. miR-497 expression was relatively decreased in breast cancer specimens and negatively correlated with TNM stage, lymphatic metastasis, tumor size and human epidermal growth factor receptor-2 (P<0.01). On the contrary, no correlation was found with estrogen receptor, progesterone receptor and p53 status. Functional assays revealed that miR-497 suppressed cellular growth, increased the percentage of early apoptotic cells and initiated G0/G1 cell phase arrest of MCF-7 cancer cells. RT-PCR and Western blot analysis data indicated that the overexpression of miR-497 resulted in the down‑regulation of Bcl-w at the mRNA and protein levels. miR-497 may serve as a tumor suppressor gene in breast cancer. The Up-regulation of miR-497 expression causes cellular growth inhibition and apoptotic enhancement, as well as G0/G1 phase arrest, suggesting its use as a potential therapeutic target for the treatment of breast cancer in the future.

Breast cancer (BC) is one of the most common malignancies among women worldwide with a high incidence of recurrence and metastasis. In this study, we demonstrate that hsa_circ_0068631, a circRNA generated from the transferrin receptor (TFRC), is upregulated in BC tissues and cell lines. Knockdown of hsa_circ_0068631 inhibited the proliferation and migration of BC cells in vitro and in vivo. Mechanistically, an RNA pull-down assay and RNA immunoprecipitation assay revealed that eukaryotic translation initiation factor 4A3 (EIF4A3) could bind to hsa_circ_0068631 and c-Myc mRNA. Additionally, the expression of hsa_circ_0068631 was positively correlated with c-Myc, and the upregulation of hsa_circ_0068631 was a crucial factor for the dysregulation of c-Myc. Through an actinomycin D assay, we confirmed that the mRNA stability of c-Myc was influenced by hsa_circ_0068631 and EIF4A3. Furthermore, hsa_circ_0068631 could recruit EIF4A3 to increase c-Myc mRNA stability. Rescue assays manifesting depletion of c-Myc rescued the promotive effect of hsa_circ_0068631 overexpression on biological activities in BC. In conclusion, to our knowledge, this study is the first to unveil the role of hsa_circ_0068631 and the hsa_circ_0068631/EIF4A3/c-Myc axis in BC, providing a new target for BC treatment.

Background: MicroRNAs (miRNAs) are small, non-coding RNAs (20–24 nucleotides) that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. The aim of this study was to investigate the expression pattern of microRNA-26b (miR-26b) in human breast cancer, and its potential role in disease pathogenesis. Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine the expression level of miR-26b in 38 breast cancer specimens and adjacent normal breast tissues. MTT assays were conducted to explore the impact of miR-26b overexpression on the proliferation of human MDA-MB-231 breast cancer cells. Luciferase reporter assays were employed to validate regulation of a putative target of miR-26b. The effect of modulating miR-26b on endogenous levels of this target were subsequently confirmed via qRT-PCR and Western blot. Results: MiR-26b expression was relatively decreased in breast cancer specimens compared with adjacent normal tissues (P<0.01). Overexpression of miR-26b suppressed MDA-MB-231 cell growth. Luciferase assays using a reporter carrying a putative miR-26b target site in the 3' untranslated region of PTGS2 revealed that miR-26b directly targets PTGS2. Overexpression of miR-26b led to downregulation of PTGS2 at the mRNA and protein level, as assessed by qRT-PCR and Western blot. Targeted knockdown of PTGS2 by siRNA significantly inhibited the proliferation of MDA-MB-231 breast cancer cells. Conclusions: MiR-26b may act as a tumor suppressor in breast cancer. The overexpression of miR-26b inhibits cellular growth by targeting PTGS2, suggesting its use as a potential therapeutic target for breast cancer.

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