Circular RNAs (circRNAs), one type of non-coding RNA, were initially misinterpreted as nonfunctional products of pre-mRNA mis-splicing. Currently, circRNAs have been proven to manipulate the functions of diverse molecules, including non-coding RNAs, mRNAs, DNAs and proteins, to regulate cell activities in physiology and pathology. Accumulating evidence indicates that circRNAs play critical roles in tumor genesis, development, and sensitivity to radiation and chemotherapy. Radiotherapy and chemotherapy are two primary types of intervention for most cancers, but their therapeutic efficacies are usually retarded by intrinsic and acquired resistance. Thus, it is urgent to develop new strategies to improve therapeutic responses. To achieve this, clarification of the underlying mechanisms affecting therapeutic responses in cancer is needed. This review summarizes recent progress and mechanisms of circRNAs in cancer resistance to radiation and chemotherapy, and it discusses the limitations of available knowledge and potential future directions.

/pdf/functions-and-mechanisms-of-circular-rnas-in-cancer-3th6tp7595.pdf

Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance

Abstract Circular RNAs (circRNAs) are a novel type of endogenous non-coding RNAs, which are covalently closed loop structures formed by precursor mRNAs (pre-mRNAs) through back-splicing. CircRNAs are abnormally expressed in many tumors, and play critical roles in a variety of tumors as oncogenes or tumor suppressor genes by sponging miRNAs, regulating alternative splicing and transcription, cis-regulating host genes, interacting with RNA binding proteins (RBPs) or encoding polypeptides. Among them, the regulation of circRNAs on their corresponding host genes is a critical way for circRNAs to exit their functions. Accumulating evidence suggests that circRNAs are able to regulate the expression of host genes at the transcriptional level, post-transcriptional level, translational level, post-translational level, or by encoding polypeptides. Therefore, this paper mainly summarized the roles and association of circRNAs and their corresponding host genes in tumorigenesis and tumor progression, generalized the circRNAs that function synergistically or antagonistically with their host genes, and elaborated the mechanisms of mutual regulation between circRNAs and their host genes. More importantly, this review provides specific references for revealing the potential application of circRNAs combined with their host genes in tumor diagnosis, treatment and prognosis. 

/pdf/understanding-the-roles-and-regulation-patterns-of-circrna-1njx7t6p.pdf

Understanding the roles and regulation patterns of circRNA on its host gene in tumorigenesis and tumor progression

Metabolic dependencies and targets in ovarian cancer.

Most tumors of the digestive system, including esophageal, gastric, liver and colorectal cancer, are malignant tumors that are associated with rates of high morbidity and mortality. The lack of effective methods for early diagnosis is an important cause of poor prognosis for these malignancies. Circular RNAs (circRNAs) belong to a family of endogenous, covalently closed non‑coding RNAs that are characterized as having no 5' cap structures or 3' poly‑A tails. Shortly following discovery, circRNAs were considered to be a product of mis‑splicing and have no significant biological function. However, in recent years, accumulating evidence is demonstrating that they serve key roles in tumorigenesis and have the potential to serve as diagnostic markers. The present article summarizes the biogenesis and function of circRNAs and reviews their role in seven common types of tumor of the digestive system whilst exploring their potential as tumor markers and the significant roles they can serve in the digestive system, in addition to providing a referencing point for future studies of digestive system malignancies.

/pdf/circular-rna-is-a-popular-molecule-in-tumors-of-the-3ic8h6x5rk.pdf

Circular RNA is a popular molecule in tumors of the digestive system (Review).

Circular RNAs (circRNAs) are a special class of endogenous RNAs with a wide variety of pathophysiological functions via diverse mechanisms, including transcription, microRNA (miRNA) sponge, protein sponge/decoy, and translation. Stem cells are pluripotent cells with unique properties of self-renewal and differentiation. Dysregulated circRNAs identified in various stem cell types can affect stem cell self-renewal and differentiation potential by manipulating stemness. However, the emerging roles of circRNAs in stem cells remain largely unknown. This review summarizes the major functions and mechanisms of action of circRNAs in stem cell biology and disease progression. We also highlight circRNA-mediated common pathways in diverse stem cell types and discuss their diagnostic significance with respect to stem cell-based therapy. 

Circular RNAs in stem cells: from basic research to clinical implications

Gastric cancer (GC), identified as the most common gastrointestinal malignancy, is one of the primary causes of cancer-related mortality in the world. Although surgery and chemotherapy for GC treatment have been improved, the 5-year overall survival rate is still unsatisfactory. Circ-NOTCH1 is a novel circular RNA derived from its host gene NOTCH1, and has not been studied in any cancers. Here we explored the potential role and mediatory mechanism of circ-NOTCH1 in GC. In this study, circ-NOTCH1 exhibited increased expression in GC tissues and cells. Suppression of circ-NOTCH1 inhibited cell migration, invasion, tumor spheroids number, and side population ratio. Circ-NOTCH1 also promoted GC growth and metastasis in vivo. Additionally, it was found that circ-NOTCH1 could bind to miR-449c-5p. Circ-NOTCH1 promoted metastasis and stemness in GC through sponging miR-449c-5p. Subsequently, MYC was identified as a downstream gene of miR-449c-5p. MYC could bind to the promoter of NOTCH1 to regulate GC progression. Furthermore, rescue assays demonstrated that NOTCH1 knockdown reversed the effects of overexpression of MYC in metastasis and stemness in AGS cells/sh-circNOTCH1. Above findings explained that circ-NOTCH1 promoted metastasis and stemness in GC by targeting miR-449c-5p/MYC/NOTCH1 axis, suggesting the possibility of circ-NOTCH1 as a therapeutic marker for GC.

miR-449c-5p availability is antagonized by circ-NOTCH1 for MYC-induced NOTCH1 upregulation as well as tumor metastasis and stemness in gastric cancer

Integrated analysis of multiomic changes and epigenetic regulation in high-grade serous ovarian cancer provides insights into the molecular characteristics of this disease, which could help improve diagnosis and treatment.

https://aacrjournals.org/cancerres/article-pdf/doi/10.1158/0008-5472.CAN-21-3819/3189652/can-21-3819.pdf

Single-Cell Dissection of the Multiomic Landscape of High-Grade Serous Ovarian Cancer

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miR-449c-5p availability is antagonized by circ-NOTCH1 for MYC-induced NOTCH1 upregulation as well as tumor metastasis and stemness in gastric cancer

Single-Cell Dissection of the Multiomic Landscape of High-Grade Serous Ovarian Cancer