Circular RNA circ0066659 functions as a competitive endogenous RNA by sponging miR-506-3p in adrenocortical carcinoma

2018 ◽  
Author(s):  
Yunze Xu ◽  
Yiran Huang
2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Zhecheng Wang ◽  
Yan Zhao ◽  
Ruimin Sun ◽  
Yu Sun ◽  
Deshun Liu ◽  
...  

Abstract p66Shc, a master regulator of mitochondrial reactive oxygen species (mtROS), is a crucial mediator of hepatocyte oxidative stress. However, its functional contribution to acetaminophen (APAP)-induced liver injury and the mechanism by which it is modulated remain unknown. Here, we aimed to assess the effect of p66Shc on APAP-induced liver injury and to evaluate if circular RNA (circRNA) functions as a competitive endogenous RNA (ceRNA) to mediate p66Shc in APAP-induced liver injury. p66Shc-, miR-185-5p-, and circ-CBFB-silenced mice were injected with APAP. AML12 cells were transfected with p66Shc, miR-185-5p, and circ-CBFB silencing or overexpression plasmids or siRNAs prior to APAP stimulation. p66Shc was upregulated in liver tissues in response to APAP, and p66Shc silencing in vivo protected mice from APAP-induced mitochondrial dynamics perturbation and liver injury. p66Shc knockdown in vitro attenuated mitochondrial dynamics and APAP-induced hepatocyte injury. Mechanically, p66Shc perturbs mitochondrial dynamics partially by inhibiting OMA1 ubiquitination. miR-185-5p, which directly suppressed p66Shc translation, was identified by microarray and bioinformatics analyses, and its overexpression attenuated mitochondrial dynamics and hepatocyte injury in vitro. Furthermore, luciferase, pull-down and RNA immunoprecipitation assays demonstrated that circ-CBFB acts as a miRNA sponge of miR-185-5p to mediate p66Shc in APAP-induced liver injury. circ-CBFB knockdown also alleviated APAP-induced mitochondrial dynamics perturbation and hepatocyte injury. More importantly, we found that the protective effects of circ-CBFB knockdown on p66Shc, mitochondrial dynamics and liver injury were abolished by miR-185-5p inhibition both in vivo and in vitro. In conclusion, p66Shc is a key regulator of APAP-induced liver injury that acts by triggering mitochondrial dynamics perturbation. circ-CBFB functions as a ceRNA to regulate p66Shc during APAP-induced liver injury, which may provide a potential therapeutic target.


Oncotarget ◽  
2019 ◽  
Vol 10 (35) ◽  
pp. 3313-3314 ◽  
Author(s):  
Lei Peng ◽  
Guanglin Chen ◽  
Zhongxian Zhu ◽  
Ziyang Shen ◽  
Chunxia Du ◽  
...  

2020 ◽  
Author(s):  
Kun Wang ◽  
Zhimin Zhou ◽  
Junping Bao ◽  
Dong Liu ◽  
Yuanbin Hu ◽  
...  

Abstract Background: More and more evidences show that non-coding RNAs are involved in neuropathic pain, however, there are few reports on the regulatory mechanism of competitive endogenous RNA (ceRNA) in neuropathic pain. The purpose of this study is to explore the possible molecular mechanisms of neuropathic pain. Methods: We collected neuropathic pain-related microarray datasets providing expression profile of circular RNAs (circRNAs) and mRNAs from the Gene Expression Omnibus (GEO) and then performed bioinformatics analysis on them. Results: The present study has identified that up-regulated circRNAs primarily regulate the activity of focal adhesion-associated biological processes and down-regulated primarily regulate the activity of metabolic-associated biological processes by means of ceRNAs. Conclusions: Our data suggest that circRNAs may be candidates for pathogenesis in neuropathic pain and may be considered as promising therapeutic targets in the future.


2021 ◽  
Vol 18 (6) ◽  
pp. 9016-9032
Author(s):  
Jie Qiu ◽  
◽  
Maolin Sun ◽  
Chuanshan Zang ◽  
Liwei Jiang ◽  
...  

<abstract> <p>&gt;This study aimed to identify potential circular RNA (circRNA), microRNA (miRNA) and mRNA biomarkers as well as their underlying regulatory mechanisms in papillary thyroid carcinoma (PTC). Three microarray datasets from the Gene Expression Omnibus database as well as expression data and clinical phenotype from The Cancer Genome Atlas (TCGA) were downloaded, followed by differential expression, functional enrichment, protein–protein interaction (PPI), and module analyses. The support vector machine (SVM)-recursive feature elimination (RFE) algorithm was used to screen the key circRNAs. Finally, the mRNA-miRNA-circRNA regulatory network and competitive endogenous RNA (ceRNA) network were constructed. The prognostic value and clinical correlations of key mRNAs were investigated using TCGA dataset, and their expression was validated using the UALCAN database. A total of 1039 mRNAs, 18 miRNAs and 137 circRNAs were differentially expressed in patients with PTC. A total of 37 key circRNAs were obtained using the SVM-RFE algorithm, whereas 46 key mRNAs were obtained from significant modules in the PPI network. A total of 11 circRNA-miRNA pairs and 40 miRNA-mRNA pairs were predicted. Based on these interaction pairs, 46 circRNA-miRNA-mRNA regulatory pairs were integrated, of which 8 regulatory pairs in line with the ceRNA hypothesis were obtained, including two circRNAs (circ_0004053 and circ_0028198), three miRNAs (miR-199a-5p, miR-199b-5p, and miR-7-5p), and five mRNAs, namely <italic>APOA2</italic>, <italic>CCL20</italic>, <italic>LPAR5</italic>, <italic>MFGE8</italic>, and <italic>TIMP1</italic>. Survival analysis showed that <italic>LPAR5</italic> expression was associated with patient survival. <italic>APOA2</italic> expression showed significant differences between metastatic and non-metastatic tumors, whereas <italic>CCL20</italic>, <italic>LPAR5</italic>, <italic>MFGE8</italic> and <italic>TIMP1</italic> showed significant differences between metastatic and non-metastatic lymph nodes. Overall, we identified several potential targets and regulatory mechanisms involved in PTC. <italic>APOA2</italic>, <italic>CCL20</italic>, <italic>LPAR5</italic>, <italic>MFGE8</italic>, and <italic>TIMP1</italic> may be correlated with PTC metastasis.</p> </abstract>


2021 ◽  
Vol 18 (6) ◽  
pp. 9806-9821
Author(s):  
Pingping Song ◽  
◽  
Jing Chen ◽  
Xu Zhang ◽  
Xiaofeng Yin ◽  
...  

<abstract> <p>Early researches have revealed that circular RNA (circRNA) had the potential of biomarkers and could affect tumor progression through regulatory networks. However, few research focused on the function of circRNA in lung adenocarcinoma and the regulation mechanism of competitive endogenous RNA. In present study, through differential expression analysis, 10 circRNAs, 98 miRNAs(microRNA) and 2497 mRNAs were screened. Based on the 10 circRNAs and related databases, a competitive endogenous RNA regulatory network (ceRNA network) containing 7 circRNAs, 13 miRNAs and 147 mRNAs was constructed. KEGG and GO analysis suggested that 147 mRNAs were obviously enriched in biological pathway related to LUAD. By constructing a PPI network, 12 hub genes were identified by MCODE. The result of survival analysis showed that 10 hub genes (BIRC5, MKI67, CENPF, RRM2, BUB1, MELK, CEP55, CDK1, NEK2, TOP2A) were significantly related to the survival of LUAD. We randomly divided 483 clinical data into two parts: train set and validation set. The train set was used for Cox regression analysis, 3 prognostic factors (stage, T, CDK1) were screened. The nomogram model was constructed based on stage, T and CDK1. The model was evaluated by ROC curve, calibration chart, Kaplan-Meier (KM) curve and validation set data. The results indicated that the model has good accuracy. Our study elucidated the regulatory mechanism of circRNA in lung adenocarcinoma, and the nomogram model also provided insight for the clinical analysis of lung adenocarcinoma.</p> </abstract>


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