Circular RNAs as Competing Endogenous RNAs in Cardiovascular and Cerebrovascular Diseases: Molecular Mechanisms and Clinical Implications

Xue, Mei; Liu, Dongliang; Xiong, Xing‐Dong

doi:10.3389/fcvm.2021.682357

Cited by 26 publications

(16 citation statements)

References 74 publications

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“…In terms of mechanism, it has been confirmed that circRNAs, as the competitive endogenous RNAs (ceR-NAs) of miRNAs, relieved the restriction of miRNAs on the expression of target genes, and thereby affected the cell biological functions [19]. This study confirmed that miR-488-3p was a candidate miRNA for circ-NT5C2 through bioinformatics analysis and related cell experiments.…”

Section: Introductionmentioning

confidence: 54%

Circ-NT5C2 stimulates FZD4 expression to promote the malignant progression of osteosarcoma by targeting miR-488-3p

et al. 2022

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Background Circ-NT5C2 has been confirmed to be highly expressed and associated to the progression of osteosarcoma (OS). However, the behind mechanism of circ-NT5C2 involvement in OS remains unclear. Methods The expression of circ-NT5C2, miR-488-3p and FZD4 was measured by quantitative real-time PCR, and the protein expression of E-cadherin, N-cadherin and FZD4 was detected by western blot. Cell counting kit 8 assay, colony formation assay and 5-ethynyl-2-deoxyuridine assay were performed to assess the cell proliferation. The cell apoptosis was measured by flow cytometry and Caspase3/Caspase9 Activity Assay Kits. Cell migration and invasion were detected by transwell assay. Dual-luciferase reporter assay and RIP assay were carried out to determine the binding relation among circ-NT5C2, miR-488-3p and FZD4. Animal experiment and immunohistochemistry analysis were conducted to explore the role of circ-NT5C2 in tumor growth in vivo. Results Comparing with controls, the expression of circ-NT5C2 and FZD4 was upregulated and miR-488-3p expression was downregulated in OS tumor tissues and cells. Circ-NT5C2 overexpression facilitated the cell proliferation and motility and induced cell apoptosis of OS cells, whereas circ-NT5C2 knockdown had the opposite effect. Besides, we also found and confirmed that circ-NT5C2 regulated cell malignant behaviors via modulating miR-488-3p/FZD4 axis in OS. Moreover, circ-NT5C2 silencing repressed the growth of xenografts in vivo. Conclusion Circ-NT5C2 upregulated FZD4 expression via sponging miR-488-3p, thus facilitating cell malignant behaviors in OS.

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Section: Introductionmentioning

confidence: 54%

Circ-NT5C2 stimulates FZD4 expression to promote the malignant progression of osteosarcoma by targeting miR-488-3p

et al. 2022

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“…As competing endogenous RNA (ceRNA) circRNAs compete with messenger RNAs (mRNAs) for microRNAs (miRNAs). By sharing common miRNA response elements (MREs), circRNAs can act as miRNA “sponges” to regulate mRNA activity targeted by normal miRNA [ 27 , 28 ]. To find a potential ceRNA network for circWDR37, we constructed the circWDR37-miRNA-mRNA network via bioinformatics.…”

Section: Resultsmentioning

confidence: 99%

hsa_circWDR37_016 Regulates Hypoxia-Induced Proliferation of Pulmonary Arterial Smooth Muscle Cells

Liang

Long

et al. 2022

Cardiovascular Therapeutics

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Pulmonary arterial hypertension (PAH) is characterized by abnormal remodeling of pulmonary vessel walls caused by excessive pulmonary arterial smooth muscle cell (PASMC) proliferation. Our previous clinical studies have demonstrated the importance of the downregulated circRNA in PAH. However, the role of upregulated circRNAs is still elusive. Here, we identified the upregulated circRNA in PAH patients, hsa_circWDR37_016 (circWDR37), as a key regulator of hypoxic proliferative disorder of pulmonary arterial smooth muscle cells (PASMCs). Quantitative real-time PCR (qRT-PCR) analysis validated that exposure to hypoxia markedly increased the circWDR37 level in cultured human PASMCs. As evidenced by flow cytometry, 5-ethynyl-2 ′ -deoxyuridine (EdU) incorporation, wound healing, and Tunel assay, silencing of endogenous circWDR37 attenuated proliferation and cell-cycle progression in hypoxia-exposed human PASMCs in vitro. Furthermore, bioinformatics and Luciferase assay showed that circWDR37 directly sponged hsa-miR-138-5p (miR-138) and was involved in the immunoregulatory and inflammatory processes of PAH. Together, these studies suggested new insights into circRNA regulated the pathology of PAH, providing a new potential therapeutic target for PAH treatment.

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“…CircRNAs have been linked to the development of a number of cardiac diseases, including atherosclerosis, myocardial damage, heart failure, and drug-induced cardiotoxicity, according to research (Min et al, 2021). The current emphasis of circ-ITCH research in cardiac diseases is ischaemia-reperfusion (I/ R) injury and doxorubicin-induced cardiotoxicity (DOXIC).…”

Section: Cardiac Diseasesmentioning

confidence: 99%

CircRNA ITCH: Insight Into Its Role and Clinical Application Prospect in Tumor and Non-Tumor Diseases

et al. 2022

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CircRNA E3 ubiquitin protein ligase (ITCH) (circRNA ITCH, circ-ITCH), a stable closed-loop RNA derived from the 20q11.22 region of chromosome 20, is a new circRNA discovered in the cytoplasm in recent decades. Studies have shown that it does not encode proteins, but regulates proteins expression at different levels. It is down-regulated in tumor diseases and is involved in a number of biological activities, including inhibiting cell proliferation, migration, invasion, and promoting apoptosis. It can also alter disease progression in non-tumor disease by affecting the cell cycle, inflammatory response, and critical proteins. Circ-ITCH also holds a lot of promise in terms of tumor and non-tumor clinical diagnosis, prognosis, and targeted therapy. As a result, in order to aid clinical research in the hunt for a new strategy for diagnosing and treating human diseases, this study describes the mechanism of circ-ITCH as well as its clinical implications.

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Circular RNAs as Competing Endogenous RNAs in Cardiovascular and Cerebrovascular Diseases: Molecular Mechanisms and Clinical Implications

Cited by 26 publications

References 74 publications

Circ-NT5C2 stimulates FZD4 expression to promote the malignant progression of osteosarcoma by targeting miR-488-3p

Circ-NT5C2 stimulates FZD4 expression to promote the malignant progression of osteosarcoma by targeting miR-488-3p

hsa_circWDR37_016 Regulates Hypoxia-Induced Proliferation of Pulmonary Arterial Smooth Muscle Cells

CircRNA ITCH: Insight Into Its Role and Clinical Application Prospect in Tumor and Non-Tumor Diseases

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