scholarly journals The Regulation Network and Clinical Significance of Circular RNAs in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Juan Xu ◽  
Xiyi Chen ◽  
Yu Sun ◽  
Yaqian Shi ◽  
Fang Teng ◽  
...  

Breast cancer is one of the most common malignant tumors in women worldwide. Circular RNA (circRNA) is a class of structurally stable non-coding RNA with a covalently closed circular structure. In recent years, with the development of high-throughput RNA sequencing, many circRNAs have been discovered and have proven to be clinically significant in the development and progression of breast cancer. Importantly, several regulators of circRNA biogenesis have been discovered. Here, we systematically summarize recent progress regarding the network of regulation governing the biogenesis, degradation, and distribution of circRNAs, and we comprehensively analyze the functions, mechanisms, and clinical significance of circRNA in breast cancer.

2019 ◽  
Author(s):  
Pengfei Yuan ◽  
Liangliang Lei ◽  
Dechun Liu

AbstractRecently, dysregulated circular RNAs (circRNAs) have been associated with the progression of numerous malignant tumors. However, the mechanism through which circRNAs participate in breast cancer (BC) remains unclear. This study was designed to illustrate the role of hsa_circ_0068033 in BC. A series of functional experiments were conducted to assess the function of hsa_circ_0068033 in the development of BC and the underlying mechanisms. The results suggested that the expression of hsa_circ_0068033 was downregulated in BC tissues, and markedly correlated with tumor size (P=0.021) and the Tumor, Node, and Metastasis stage (P=0.023). Receiver operating characteristic analysis showed that hsa_circ_0068033 testing yielded an area under the curve value of 0.8480 in discriminating BC from non-tumor controls. Functionally, overexpression of hsa_circ_0068033 could inhibit the growth, clone formation, invasion, and migration of MCF-7 and MDA-MB-231 cells, while activating the intrinsic apoptotic pathway to induce apoptosis. The xenograft experiment revealed that exogenous hsa_circ_0068033 is able to reduce the tumorigenic ability of MDA-MB-231 cells in nude mice. Rescue assays further proved that hsa_circ_0068033 exerts biological functions by sponging miR-659. This study revealed for the first time that hsa_circ_0068033 acts as a tumor suppressor gene in BC, and the hsa_circ_0068033/miR-659 axis participates in the progression of BC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiabin Yu ◽  
Li Yang ◽  
Hongting Lu

AbstractMalignant tumors are one of the fatal diseases that threaten children’s physical and mental health and affect their development. Research has shown that the occurrence and development of malignant tumors are associated with the abnormal expression and regulation of genes. Circular RNAs (circRNAs) are noncoding RNAs that have a closed circular structure, with a relatively stable expression, and do not undergo exonuclease-mediated degradation readily. Recent studies have shown that circRNA plays an important role in the occurrence, metastasis, and invasion of solid malignant tumors (SMTs) in children. Thus, circRNA is being considered as a breakthrough in the treatment of SMTs in children. In this review, we describe the functions and mechanisms of circRNAs involved in SMTs in children oncogenesis, and summarize the roles of circRNAs in regulating cell proliferation, cell apoptotic death, the cell cycle, cell migrative and invasive ability, epithelial-mesenchymal transition (EMT), cancer stem cells and drug resistance in SMTs in children. In addition, we also discuss the role of circRNAs in the early diagnosis, pathological grading, targeted therapy, and prognosis evaluation of common SMTs in children. CircRNAs are likely to provide a novel direction in therapy in SMTs of children.


2020 ◽  
Author(s):  
Nan Zhang ◽  
Yue Jin ◽  
Qiubo Hu ◽  
Shanshan Cheng ◽  
Chao Wang ◽  
...  

Abstract Background: Increasing researches have demonstrated the critical functions of circular RNAs (circRNAs) in the progression of malignant tumors, including ovarian cancer. In this study, we aim to investigate abnormally expression of hsa_circ_0078607 and the role of hsa_circ_0078607 during ovarian cancer pathogenesis.Methods: RT-PCR were used to detect the expression of circ_0078607 in ovarian cancer tissues. To determine the functional roles of circ_0078607 in ovarian cancer, cell proliferation and cell invasion assays were performed. Bioinformatics and luciferase reporter analysis were used to predict the target of circ_0078607.Results: In the present study, we first found that circ_0078607 was downregulated in ovarian cancer. Forced circ_0078607 expression significantly suppressed proliferation and promotes apoptosis of ovarian cancer cells. Mechanically, bioinformatics and luciferase reporter analysis identified that miR-518a-5p as a direct target of circ_0078607, while Fas as a direct target of miR-518a-5p. MiR-518a-5p negatively regulates Fas in ovarian cancer cells, while overexpression of circ_0078607 could increase the expression of Fas inhibited by miR-518a-5p. Furthermore, overexpression of circ_0078607 could inhibit the proliferation and invasion of ovarian cancer cells caused by miR-518a-5p mimic.Conclusion: The results of the present study revealed that circ_0078607 suppresses ovarian cancer progression by sponging oncogenic miR-518a-5p to induce Fas expression, which may provide new therapeutic approach for ovarian cancer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Siying Wang ◽  
Zhenyao Chen ◽  
Jingyao Gu ◽  
Xin Chen ◽  
Zhaoxia Wang

Long non-coding RNA (lncRNA) PCAT6 is a member of the Prostate Cancer Associated Transcripts family of molecules. In this review, we focus on the latest studies involving PCAT6 in the diagnosis, treatment, and prognosis of malignant tumors of the digestive, respiratory, urinary, reproductive, motion, and nervous systems. PCAT6 was found to be highly expressed in gastric cancer, colon cancer, hepatocellular carcinoma, lung cancer, bladder cancer, ovarian cancer, breast cancer, cervical cancer, osteosarcoma, glioblastoma, and other tumors. PCAT6 can promote the development and progression of different types of malignant tumors through various mechanisms. Overall, these findings suggest that PCAT6 may play an increasingly vital role in the clinical assessment of these malignant tumors. It can function as an oncogene and may be used as a potential new prognostic biomarker of these tumors.


Author(s):  
Yalan Ma ◽  
Lianwen Zheng ◽  
Yiyin Gao ◽  
Wenying Zhang ◽  
Qiang Zhang ◽  
...  

Circular RNA (circRNA) is a highly conserved, stable and abundant non-coding RNA (ncRNA). Also, some circRNAs play an essential part in the progression of human cancers. CircRNA is different from traditional linear RNA. CircRNA has a closed circular structure, so it is resistant to exonuclease-mediated degradation and is more stable than linear RNA. Numerous studies have found that many circRNAs can act as a microRNA (miRNA) sponge, interact with RNA-binding proteins, regulate gene transcription, affect alternative splicing and be translated into proteins. Recently, some studies have also indicated that circRNA participates in the progression of gynecological cancers. In addition, circRNA can act as a promising biomarker for the diagnosis of gynecological tumors. Additionally, they can also play a key role in the prognosis of gynecological tumors. Furthermore, to our delight, circRNA may be a potential therapeutic target in gynecological cancers and widely used in clinical practice. This article reviews the functions and related molecular mechanisms of circRNAs in gynecological tumors, and discusses their potential as biomarkers for diagnostic and prognostic and therapeutic targets for gynecological cancers.


2021 ◽  
Author(s):  
Aihong Wang ◽  
Canhui Jin ◽  
Ying Wang ◽  
Juanjuan Yu ◽  
Ruifang Wang ◽  
...  

Abstract BackgroundCircular RNAs (circRNAs), a new type of non-coding RNA, have been demonstrated to play critical roles in the progression of various of malignant cancers. In the present study, we identified a circRNA termed as circTADA2A which was hypothesized that may be significantly up-regulated in OC tissues and cell lines.ResultsThe results revealed that ectopic expression of circTADA2A promoted the cell proliferation, migration, invasion and colony formation ability of OC cells. Constantly, silencing of circTADA2A inhibited those of OC cells. Furthermore, we identified that circTADA2A was able to target miR-203 in OC cell. MiR-203 was able to reverse the oncogenic effect of circTADA2A on proliferation, migration and metastasis of OC cells through targeting SMAD1.ConclusionsWe reported that circTADA2A served as a competing endogenous RNA (ceRNA) to sponge miR-203 and blocked its regulation of SMAD1. These findings provide insights into OC progression and also potential new targets for diagnose or treatment of OC.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2595
Author(s):  
Chen Bian ◽  
Xiu-Juan Lei ◽  
Fang-Xiang Wu

CircRNAs (circular RNAs) are a class of non-coding RNA molecules with a closed circular structure. CircRNAs are closely related to the occurrence and development of diseases. Due to the time-consuming nature of biological experiments, computational methods have become a better way to predict the interactions between circRNAs and diseases. In this study, we developed a novel computational method called GATCDA utilizing a graph attention network (GAT) to predict circRNA–disease associations with disease symptom similarity, network similarity, and information entropy similarity for both circRNAs and diseases. GAT learns representations for nodes on a graph by an attention mechanism, which assigns different weights to different nodes in a neighborhood. Considering that the circRNA–miRNA–mRNA axis plays an important role in the generation and development of diseases, circRNA–miRNA interactions and disease–mRNA interactions were adopted to construct features, in which mRNAs were related to 88% of miRNAs. As demonstrated by five-fold cross-validation, GATCDA yielded an AUC value of 0.9011. In addition, case studies showed that GATCDA can predict unknown circRNA–disease associations. In conclusion, GATCDA is a useful method for exploring associations between circRNAs and diseases.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sheng Gao ◽  
Xun Lu ◽  
Jingjing Ma ◽  
Qian Zhou ◽  
RanRan Tang ◽  
...  

Breast cancer is one of the most common malignant tumors in women and is the second leading cause of cancer deaths among women. The tumorigenesis and progression of breast cancer are not well understood. The existing researches have indicated that non-coding RNAs, which mainly include long non-coding RNA (lncRNA) and microRNA (miRNA), have gradually become important regulators of breast cancer. We aimed to screen the differential expression of miRNA and lncRNA in the different breast cancer stages and identify the key non-coding RNA using TCGA data. Based on series test of cluster (STC) analysis, bioinformatics analysis, and negatively correlated relationships, 122 lncRNAs, 67 miRNAs, and 119 mRNAs were selected to construct the regulatory network of lncRNA and miRNA. It was shown that the miR-93/20b/106a/106b family was at the center of the regulatory network. Furthermore, 6 miRNAs, 10 lncRNAs, and 15 mRNAs were significantly associated with the overall survival (OS, log-rank P < 0.05) of patients with breast cancer. Overexpressed miR-93 in MCF-7 breast cancer cells was associated with suppressed expression of multiple lncRNAs, and these downregulated lncRNAs (MESTIT1, LOC100128164, and DNMBP-AS1) were significantly associated with poor overall survival in breast cancer patients. Therefore, the miR-93/20b/106a/106b family at the core of the regulatory network discovered by our analysis above may be extremely important for the regulation of lncRNA expression and the progression of breast cancer. The identified key miRNA and lncRNA will enhance the understanding of molecular mechanisms of breast cancer progression. Targeting these key non-coding RNA may provide new therapeutic strategies for breast cancer treatment and may prevent the progression of breast cancer from an early stage to an advanced stage.


2021 ◽  
Vol 27 (2) ◽  
pp. 3793-3798
Author(s):  
Yordanka Doneva ◽  
◽  
Veselin Valkov ◽  
Yavor Kashlov ◽  
Galya Mihaylova ◽  
...  

Circular RNA (circRNAs) belong to the long non-coding RNA family, but unlike the linear RNA in circular RNA, the 3’ and 5’ end in the RNA molecule are joined together, forming their circular structure. Until recently, circRNAs have been believed to be a side product of splicing, but now it is known that they have a wide range of biological functions, from regulators of gene expression to regulators of other non-coding RNAs - microRNAs (miRNAs). CircRNAs have the potential of being therapeutic targets and biomarkers for diseases. There are little data and only several investigations about this type of RNAs in myocardial infarction in humans. This review summarizes the role of some new circRNA – miRNA interactions in the development of Myocardial Infarction.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yixiang Huang ◽  
Wenfang Zheng ◽  
Changle Ji ◽  
Xuehui Wang ◽  
Yunhe Yu ◽  
...  

AbstractBreast cancer (BC) is one of the most fatal diseases among women all over the world. Non-coding RNAs including circular RNAs (circRNAs) have been reported to be involved in different aspects during tumorigenesis and progression. In this study, we aimed to explore the biological functions and underlying mechanism of circRPPH1 in BC. Candidate circRNAs were screened in dataset GSE101123 from Gene Expression Omnibus (GEO) database and a differentially expressed circRNA, circRPPH1, was discovered in BC. CircRPPH1 expression was higher in the cancerous tissue compared to paired adjacent tissue. Further in vitro and in vivo experiments indicated that circRPPH1 acted as an oncogene in BC. In addition, circRPPH1 was mainly localized in cytoplasm and played the role of miR-512-5p sponge. By sequestering miR-512-5p from the 3′-UTR of STAT1, circRPPH1 inhibited the suppressive role of miR-512-5p, stabilized STAT1 mRNA in BC and finally affected BC progression. In conclusion, these findings indicated that circRPPH1 acted as an oncogene and regulated BC progression via circRPPH1-miR-512-5p-STAT1 axis, which might provide a potential therapeutic target for BC treatment.


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