Circular RNAs (circRNAs) are a class of long, non-coding RNAs molecules that shape a covalently closed continuous loop which have no 5'-3' polarity and contain no polyA tail. CircRNAs also possess relatively jarless framework and are highly tissue-specific expressed in the eukaryotic transcriptome. Emerging evidences have discovered that thousands of endogenous circRNAs are present in mammalian cells and they mediate gene expression at the transcriptional or post-transcriptional level by binding to microRNAs or other molecules and then inhibit their function. Similarly, increasing evidence indicates that circRNAs may play a role in the development of several types of diseases, including atherosclerotic vascular disease risk, neurological disorders, prion diseases, osteoarthritis and diabetes. Furthermore, circRNAs exhibit aberrant expression in multiform types of cancer, including colorectal cancer, hepatocellular carcinoma and pancreatic ductal adenocarcinoma. And based on the function of circRNAs in cancer, we believe that circRNAs may serve as diagnostic or tumor promising biomarkers. Moreover, it will provide a new therapeutic target for the treatment of cancer.

No abstract

Circular RNAs (circRNAs) are recently regarded as a naturally forming family of widespread and diverse endogenous noncoding RNAs (ncRNAs) that may regulate gene expression in mammals. At present, above 30000 circRNAs have already been found, with their unique structures to maintain stability more easily than linear RNAs. Several previous literatures stressed on the important role of circRNAs, whose expression was relatively correlated with patients’ clinical characteristics and grade, in the carcinogenesis of cancer. CircRNAs are involved in many regulatory bioprocesses of malignance, including cell cycle, tumorigenesis, invasion, metastasis, apoptosis, vascularization, through adsorbing RNA as a sponge, binding to RNA-binding protein (RBP), modulating transcription, or influencing translation. Therefore, it is inevitable to further study the interactions between circRNAs and tumors and to develop novel circRNAs as molecular markers or potential targets, which will provide promising applications in early diagnosis, therapeutic evaluation, prognosis prediction of tumors and even gene therapy for tumors.

Pathological cardiac hypertrophy is a key risk factor for heart failure. It is associated with increased interstitial fibrosis, cell death and cardiac dysfunction. The progression of pathological cardiac hypertrophy has long been considered as irreversible. However, recent clinical observations and experimental studies have produced evidence showing the reversal of pathological cardiac hypertrophy. Left ventricle assist devices used in heart failure patients for bridging to transplantation not only improve peripheral circulation but also often cause reverse remodeling of the geometry and recovery of the function of the heart. Dietary supplementation with physiologically relevant levels of copper can reverse pathological cardiac hypertrophy in mice. Angiogenesis is essential and vascular endothelial growth factor (VEGF) is a constitutive factor for the regression. The action of VEGF is mediated by VEGF receptor-1, whose activation is linked to cyclic GMP-dependent protein kinase-1 (PKG-1) signaling pathways, and inhibition of cyclic GMP degradation leads to regression of pathological cardiac hypertrophy. Most of these pathways are regulated by hypoxia-inducible factor. Potential therapeutic targets for promoting the regression include: promotion of angiogenesis, selective enhancement of VEGF receptor-1 signaling pathways, stimulation of PKG-1 pathways, and sustention of hypoxia-inducible factor transcriptional activity. More exciting insights into the regression of pathological cardiac hypertrophy are emerging. The time of translating the concept of regression of pathological cardiac hypertrophy to clinical practice is coming.

Circular RNAs (circRNAs) are increasingly gaining importance and attention due to their diverse potential functions and their value as diagnostic biomarkers (disease specific). This study aims to explore the novel mechanisms by which exosome-contained circRNAs promote tumor development and metastasis in TNBC. We identified increased circRNA circPSMA1 in TNBC cells, their exosomes, and serum exosomes samples from TNBC patients. The overexpression of circPSMA1 promoted TNBC cell proliferation, migration, and metastasis both in vitro and in vivo. Moreover, we investigated the tumor-infiltrating immune cells (TICs) or stromal components in immune microenvironment (IME), and identified the significant differences in the immune cells between TNBC and non-TNBC samples. Mechanistically, circPSMA1 acted as a “miRNAs sponge” to absorb miR-637; miR-637 inhibited TNBC cell migration and metastasis by directly targeted Akt1, which recognized as a key immune-related gene and affected downstream genes β-catenin and cyclin D1. Subsequent co-culture experiments also demonstrated that exosomes from TNBC carrying large amounts of circPSMA1 could transmit migration and proliferation capacity to recipient cells. Kaplan–Meier plots showed that high expression of Akt1 and low expression of mir-637 are highly correlated with poor prognosis in patients with lymph node metastasis of TNBC. Collectively, all these results reveal that circPSMA1 functions as a tumor promoter through the circPSMA1/miR-637/Akt1-β-catenin (cyclin D1) regulatory axis, which can facilitate the tumorigenesis, metastasis, and immunosuppression of TNBC. Our research proposes a fresh perspective on novel potential biomarkers and immune treatment strategies for TNBC.