Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma

109

Background/Aims: Circular RNAs (circRNAs), a type of RNA that is widely expressed in human cells, have essential roles in the development and progression of cancer. CircRNAs contain microRNA (miRNA) binding sites and can function as miRNA sponges to regulate gene expression by removing the inhibitory effect of an miRNA on its target gene. Methods: We used the bioinformatics software TargetScan and miRanda to predict circRNA-miRNA and miRNAi-Mrna interactions. Rate of inhibiting of proliferation was measured using a WST-8 cell proliferation assay. Clone formation ability was assessed with a clone formation inhibition test. Cell invasion and migration capacity was evaluated by performing a Transwell assay. Relative gene expression was assessed using quantitative real-time polymerase chain reaction and relative protein expression levels were determined with western blotting. circRNA and miRNA interaction was confirmed by dual-luciferase reporter and RNA-pull down assays. Results: In the present study, the miRNA hsa-miR-21-5p was a target of circRNA-ACAP2, and T lymphoma invasion and metastasis protein 1 (Tiam1) was identified as a target gene of hsa-miR-21-5p. CircRNA-ACAP2 and Tiam1 were shown to be highly expressed in colon cancer tissue and colon cancer SW480 cells, but miR-21-5p was expressed at a low level. SW480 cell proliferation was suppressed when the expression of circRNA-ACAP2 and Tiam1 was decreased and the expression of miR-21-5p was increased in vivo and in vitro. SW480 cell migration and invasion were also inhibited under the same circumstance. The circRNA-ACAP2 interaction regulated the expression of miR-21-5p, and miR-21-5p regulated the expression of Tiam1. Down-regulation of circRNA-ACAP2 promoted miR-21-5p expression, which further suppressed the transcription and translation of Tiam1. Conclusion: The present study shows that the circRNA-ACAP2/hsa-miR-21-5p/Tiam1 regulatory feedback circuit could affect the proliferation, migration, and invasion of colon cancer SW480 cells. This was probably due to the fact that circRNA-ACAP2 could act as a miRNA sponge to regulate Tiam1 expression by removing the inhibitory effect of miR-21-5p on Tiam1 expression. The results from this study have revealed new insights into the pathogenicity of colon cancer and may provide novel therapeutic targets for the treatment of colon cancer.

Section: Discussionmentioning

confidence: 99%

The CircRNA-ACAP2/Hsa-miR-21-5p/ Tiam1 Regulatory Feedback Circuit Affects the Proliferation, Migration, and Invasion of Colon Cancer SW480 Cells

Han

et al. 2018

109

“…These properties give circRNAs the potential of being ideal biomarkers for human diseases. Recent studies have revealed that circRNAs can be used as diagnostic or predictive biomarkers for hepatocellular carcinoma [11], pre-eclampsia [22], gastric cancer [23], and bladder cancer [24]. However, little is known about the role of circRNAs in RA.…”

Section: Discussionmentioning

confidence: 99%

Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Rheumatoid Arthritis Patients

Ouyang

Jiang

et al. 2017

138

102

Background/Aims: Circular RNAs (circRNAs) compose a large class of RNAs that can be used as biomarkers in clinical blood samples. This study aimed to determine the expression of circRNAs in peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis (RA) patients to identify novel biomarkers for RA screening. Methods: We started with a microarray screening of circRNA changes in PBMCs from 5 RA patients and 5 healthy controls. We then confirmed the selected circRNA changes in PBMCs from 30 RA patients and 25 age- and sex-matched controls using the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spearman correlation test was performed to assess the correlation of circRNAs and clinical variables. Receiver operating characteristic (ROC) curve was calculated to evaluate the diagnostic value. Results: We identified and verified five circRNAs (092516, 003524, 103047, 104871, 101873) that were significantly elevated in PBMCs from RA patients. Among these RA patients, we detected no significant correlation between the five circRNAs and the disease severity, including disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and health assessment questionnaire (HAQ). Yet, ROC curve analysis suggested that circRNA_104871 has significant value of RA diagnosis (AUC=0.833, P<0.001), followed by circRNA_003524 (AUC = 0.683, P = 0.020), circRNA_101873 (AUC = 0.676, P = 0.026), and circRNA_103047 (AUC = 0.671, P = 0.030). Conclusions: This study suggests that increased expression of circRNAs circRNA_104871, circRNA_003524, circRNA_101873 and circRNA_103047 in PBMC from RA patients may serve as potential biomarkers for RA patient diagnosis.

“…Similarly, cir-ITCH inhibits the proliferation of ESCC by sponging miR-7, miR-17 and miR-214. To date, only two studies [30, 31] have revealed the altered expression of circRNAs in bladder cancer, indicating that circRNAs play important roles in the development and progression of bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

CircRNA-Cdr1as Exerts Anti-Oncogenic Functions in Bladder Cancer by Sponging MicroRNA-135a

Yang

Yuan

et al. 2018

132

108

Background/Aims: CircRNAs regulate gene expression in different malignancies. However, the role of Cdr1as in the tumourigenesis of bladder cancer and its potential mechanisms remain unknown. Methods: qRT-PCR was used to detect Cdr1as and target miRNA expression in bladder cancer tissues and cell lines. Biological functional experiments were performed to detect the effects of Cdr1as on the biological behaviour of bladder cancer cells in vivo and in vitro. Bioinformatic analysis was utilised to predict potential miRNA target sites on Cdr1as. Ago2 RNA binding protein immunoprecipitation assay, RNA antisense purification assay, biotin pull down assay and RNA FISH were performed to detect the interaction between Cdr1as and target miRNAs. Western blot was used to determine the expression level of p21 in bladder cancer cells. Results: Cdr1as was significantly down-regulated in bladder cancer tissues compared with adjacent normal tissues. Overexpression of Cdr1as inhibited the proliferation, invasion and migration of bladder cancer cells in vitro and slowed down tumour growth in vivo. Cdr1as sponged multiple miRNAs in bladder cancer. Moreover, Cdr1as directly bound to miR-135a and inhibited its activity in bladder cancer. Conclusion: Cdr1as is down-regulated and sponges multiple miRNAs in bladder cancer. It exerts anti-oncogenic functions by sponging microRNA-135a.