Emerging Epigenetic Regulation of Circular RNAs in Human Cancer

Wu, Jie; Qi, Xiaoqian; Liu, Lina; Hu, Xin; Li, Jingwen; Yang, Jianming; Yang, Jun; Lu, Lu; Zhang, Zheng; Ma, Shiqing; Li, Hongfa; Yun, Xinyue; Sun, Tong; Wang, Yue; Wang, Zuomin; Liu, Zihao; Zhao, Wei

doi:10.1016/j.omtn.2019.04.011

Cited by 178 publications

(119 citation statements)

References 69 publications

(116 reference statements)

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“…Circ‐RNA, unlike linear RNAs, features a closed‐loop structure . This distinctive structure contributes to the ability of circRNA to resist the activity of exonuclease to a certain extent, so that it can exist stably in cells . CircRNA has been gradually recognized as a new clinical biomarker and potential therapeutic target .…”

Section: Introductionmentioning

confidence: 99%

Circ_0001658 promotes the proliferation and metastasis of osteosarcoma cells via regulating miR‐382‐5p/YB‐1 axis

Wang

et al. 2019

Cell Biochemistry & Function

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Circular RNA (circRNA) can modulate the gene expression via sponging microRNA (miRNA) in multiple malignancies. Nevertheless, the detailed function of circ_0001658 in osteosarcoma (OS) and its regulatory mechanism remain elusive.Real-time PCR was carried out to detect the expressions of circ_0001658, miR-382-5p, and Y box-binding protein 1 (YB-1) mRNA in OS tissues. Besides, western blot was done to monitor YB-1 expression in OS cells. Chi-squared test was used to analyse the correlation between circ_0001658 and clinicopathologic characteristics of OS patients. CCK8 assay, colony formation assay, flow cytometry, and transwell assay were performed to determine the function of circ_0001658. Moreover, dualluciferase reporter gene assay was done to verify the targeting relationship between circ_0001658 and miR-382-5p. Compared with adjacent tissues, circ_0001658 displayed a significantly higher expression in OS tissues. Circ_0001658 could facilitate the proliferation, migration, and invasion of OS cells and impede apoptosis by sponging miR-382-5p. Further, circ_0001658 was proved to directly and negatively regulate the expression of miR-382-5 while positively modulate the expression of YB-1. Circ_0001658 promotes the proliferation and metastasis of OS cells via modulating miR-382-5p/YB-1 axis. Significance of the study:In recent years, the expression and function of circular RNA in cancer have been the focus of tumour research. The study on circular RNA helps elucidate the molecular pathology of tumorigenesis and cancer progression.This study demonstrated that circ_0001658 promotes the proliferation and metastasis of OS cells via modulating miR-382-5p/YB-1 axis. To our best knowledge, this work is the first to study the expression and function of circ_0001658 in cancer. K E Y W O R D Scirc_0001658, miR-382-5p, osteosarcoma, YB-1 | INTRODUCTIONOsteosarcoma (OS) is a common primary malignant bone tumour among children and adolescents, frequently diagnosed in the distal femur, the proximal tibia, and the proximal humerus. 1,2 Though multiple treatments offer symptomatic relief and modest improvement in survival for OS patients, the long-term disease-free survival rate of patients remains unfavourable, only 60% to 75%. 3,4 To make matters worse, the 5-year survival rate was only 27% to 55% in patients with local relapsing and distant metastasis treated by the available therapy clinically. 5 Hence, it is imperative to probe into the detailed mechanism of OS.Circular RNA (circRNA) is a novel class of endogenous noncoding RNA, which exists widely and stably in mammalian cells without the function of encoding proteins. 6,7 Circ-RNA, unlike linear RNAs, features a closed-loop structure. 8 This distinctive structure contributes

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Section: Introductionmentioning

confidence: 99%

Circ_0001658 promotes the proliferation and metastasis of osteosarcoma cells via regulating miR‐382‐5p/YB‐1 axis

Wang

et al. 2019

Cell Biochemistry & Function

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“…CircRNAs can be detectable in body fluids, such as blood and saliva, urine, and breast milk including membrane-bound vesicles, such as exosome, and has widely involved in a variety of cancer-related physiological and pathology processes, including cancer initiation, progression and metastasis, drug resistance and played an important role in the diagnostic and prognostic biomarker and the therapeutic target in human cancer. [245][246][247] It has become increasingly clear that circRNAs regulate gene expression through various actions and play diverse roles in many fields of human cancer biology. Recently, investigating the presence and expression levels of exosomal circRNAs could allow us to discriminate cancer patients from healthy individuals, identifying new potential exosome-based cancer biomarkers.…”

Section: Discussion and Prospectivementioning

confidence: 99%

<p>Biological Roles and Mechanisms of Circular RNA in Human Cancers</p>

Tang

Hann

2020

OTT

133

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Circular RNA (circRNA) is an intriguing class of RNA with covalently closedloop structure and is highly stable and conservative. As new members of the ncRNAs, the function, mechanism, potential diagnostic biomarker, and therapeutic target have raised increased attention. Most circRNAs are presented with characteristics of abundance, stability, conservatism, and often exhibiting tissue/developmental-stage-specific manner. Over 30,000 circRNAs have been identified with their unique structures to maintain stability more easily than linear RNAs. An increased numbers of circRNAs are dysregulated and involved in several biological processes of malignance, such as tumorigenesis, growth, invasion, metastasis, apoptosis, and vascularization. Emerging evidence suggests that circRNAs play important roles by acting as miRNA sponge or protein scaffolding, autophagy regulators, and interacting with RNA-binding protein (RBP), which may potentially serve as a novel promising biomarker for prevention, diagnosis and therapeutic target for treatment of human cancer with great significance either in scientific research or clinic arena. This review introduces concept, major features of circRNAs, and mainly describes the major biological functions and clinical relevance of circRNAs, as well as expressions and regulatory mechanisms in various types of human cancer, including pathogenesis, mode of action, potential target, signaling regulatory pathways, drug resistance, and therapeutic biomarkers. All of which provide evidence for the potential utilities of circRNAs in the diagnosis and treatment of cancer.

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“…[9][10][11][12] CircRNAs can affect the regulation of gene expression through acting as competing endogenous RNA (ceRNAs) with the characteristics of stable structure, abundance, and tissue/developmental-stage-specific expression. A, The expression levels of hsa_ circ_0067582 in cancer tissues (n = 96) and adjacent normal tissues (n = 96).…”

Section: Discussionmentioning

confidence: 99%

“…Higher Δ Ct value indicates lower expression (*P < .05, **P < .01, ***P < .001) functionless by-products and have become a new hot topic in very recent years with the RNA-seq technology of next-generation sequencing development. [9][10][11][12] CircRNAs can affect the regulation of gene expression through acting as competing endogenous RNA (ceRNAs) with the characteristics of stable structure, abundance, and tissue/developmental-stage-specific expression. 10,11 Previous studies demonstrated that circRNAs existed widely in all kinds of organizations and exhibit abnormal expression levels in digestive system cancers.…”

Section: Discussionmentioning

confidence: 99%

Clinical significances of hsa_circ_0067582 and hsa_circ_0005758 in gastric cancer tissues

Shao

et al. 2019

Clinical Laboratory Analysis

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Background Circular RNAs (circRNAs) are a special class of endogenous noncoding RNAs that have numerous biological functions in normal situation and diseases including cancers. However, the clinical significance of circRNAs in gastric cancer (GC) remains largely unknown. Here, we chose two representative circRNAs, hsa_circ_0067582 and hsa_circ_0005758, to investigate their clinical significance in GC patients. Methods Using real‐time quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR), we explored the expression levels of hsa_circ_0067582 and hsa_circ_0005758 in tissues with different stages of gastric tumorigenesis. Then, the relationships between their expression levels and GC patients' clinicopathological factors were further investigated. Receiver operating characteristic (ROC) curves were established for evaluating diagnostic values of hsa_circ_0067582 and hsa_circ_0005758. Results Compared with healthy control tissues, both hsa_circ_0067582 and hsa_circ_0005758 were significantly decreased in GC tissues. Besides, hsa_circ_0067582 expression was associated with GC patients' tissue CEA level (P <.001) and stages (P = .037); and hsa_circ_0005758 expression was relevant to tissue CEA level (P < .001) and perineural invasion (P = .048). The area under the ROC curve (AUC) of hsa_circ_0067582 was up to 0.671. The cutoff value was set at 10.61, with which the sensitivity and specificity were 55.2% and 75.0%, respectively. Similar to hsa_circ_0005758, the AUC of hsa_circ_0005758 was 0.721. The cutoff value was set at 10.20, with which the sensitivity and specificity were 75.0% and 67.7%, respectively. Conclusion These results showed that both hsa_circ_0067582 and hsa_circ_0005758 may play an important role in gastric carcinogenesis; and they may be potential indicators for GC diagnosis.

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Emerging Epigenetic Regulation of Circular RNAs in Human Cancer

Cited by 178 publications

References 69 publications

Circ_0001658 promotes the proliferation and metastasis of osteosarcoma cells via regulating miR‐382‐5p/YB‐1 axis

Circ_0001658 promotes the proliferation and metastasis of osteosarcoma cells via regulating miR‐382‐5p/YB‐1 axis

<p>Biological Roles and Mechanisms of Circular RNA in Human Cancers</p>

Clinical significances of hsa_circ_0067582 and hsa_circ_0005758 in gastric cancer tissues

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