Current Status of Functional Studies on Circular RNAs in Bladder Cancer and their Potential Role as Diagnostic and Prognostic Biomarkers: A Review

Liu, Cong; Yang, Qiwei; Hu, Chunmei; Yu, Qiong; Hao, Shuhong; Li, Dongfu

doi:10.12659/msm.916697

Cited by 16 publications

(12 citation statements)

References 95 publications

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“…Disease-specific expression of circRNAs made them available as molecular markers for the treatment of cancers [ 6 ]. Additionally, circRNAs were enrolled in the evolution of diverse cancers [ 7 ], such as gastric carcinoma [ 8 ], breast cancer [ 9 ], lung carcinoma [ 10 ] and bladder cancer [ 11 ]. As previously reported, circ_0066147 contributed to cell growth and metastasis via upregulating p21-activated kinase 1 (PAK1) through acting as a sponge for miR-330-5p in pancreatic cancer [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Circ-MBOAT2 knockdown represses tumor progression and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer

Zhou

Liu

Cui

et al. 2021

J Exp Clin Cancer Res

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Background Pancreatic cancer is a malignant tumor and ranks the sixth in incidence among cancers. Circular RNA (circRNA) has been reported to regulate the progression of pancreatic cancer. However, the effects of circ-membrane bound O-acyltransferase domain containing 2 (circ-MBOAT2) on regulating pancreatic cancer process were unclear. Methods The expression levels of circ-MBOAT2, microRNA-433-3p (miR-433-3p) and glutamic-oxaloacetic transaminase 1 (GOT1) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). GOT1 protein expression was determined by western blot analysis. Cell proliferation was illustrated by 3-(4,5)-dimethylthiahiazo (−z-y1)-3,5-di-phenytetrazoliumromide (MTT) and cell colony formation assay. Cell apoptosis was demonstrated by flow cytometry analysis. Cell invasion and migration were investigated by transwell invasion and wound-healing assays. Glutamine catabolism was explained by detecting glutamine consumption, alpha ketoglutarate (α-KG) production and glutamate production. In vivo assay was performed to illustrate the impacts of circ-MBOAT2 silencing on tumor formation in vivo. The binding relationship between miR-433-3p and circ-MBOAT2 or GOT1 was predicted by circinteractome or starbase online databases, and identified by dual-luciferase reporter assay. Results Circ-MBOAT2 and GOT1 expression were significantly upregulated, while miR-433-3p expression was downregulated in pancreatic cancer tissues and cells compared with normal pancreatic tissues or cells. Circ-MBOAT2 silencing repressed cell proliferation, migration, invasion and glutamine catabolism, whereas promoted cell apoptosis in pancreatic cancer. Additionally, circ-MBOAT2 acted as a sponge of miR-433-3p, which was found to be associate with GOT1. MiR-433-3p inhibitors hindered circ-MBOAT2 silencing-mediated impacts on pancreatic cancer progression and glutamine catabolism. Furthermore, circ-MBOAT2 silencing repressed tumor formation in vivo. Conclusion Circ-MBOAT2 modulated tumor development and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer. This finding suggests that circ-MBOAT2 may be a therapeutic target for pancreatic cancer.

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Section: Introductionmentioning

confidence: 99%

Circ-MBOAT2 knockdown represses tumor progression and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer

Zhou

Liu

Cui

et al. 2021

J Exp Clin Cancer Res

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“…Over the past decades, emerging circRNAs have been found to be involved in the regulation of cancer progression by acting as the molecular sponges of miRNAs. 4 , 19 Prior studies also showed that circCEP128 could exert its oncogenic effect by sponging miR-145-5p in bladder cancer. 9 , 10 In this study, we demonstrated that circCEP128 could negatively regulate miR-515-5p expression by direct interaction in bladder cancer cells.…”

Section: Discussionmentioning

confidence: 99%

circCEP128 Knockdown Suppresses Bladder Cancer Progression via Regulating microRNA-515-5p/SDC1 Axis

Cao¹,

Zhang²,

Tian³

et al. 2021

CMAR

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Background: Dysregulation of circular RNAs (circRNAs) is associated with bladder cancer progression. Nevertheless, the mechanisms of circRNA centrosomal protein 128 (circCEP128) underlying bladder cancer progression remain poorly understood. Methods: The levels of circCEP128, microRNA-515-5p (miR-515-5p) and syndecan-1 (SDC1) were determined via reverse transcription-quantitative polymerase chain reaction or Western blot. The effects of circCEP128, miR-515-5p and SDC1 on bladder cancer progression were investigated via MTT and colony formation assays, flow cytometry and transwell analysis and subcutaneous xenograft experiments. The interactions between miR-515-5p and circCEP128 or SDC1 were examined through bioinformatics prediction and luciferase reporter assay. Results: circCEP128 and SDC1 were highly expressed and miR-515-5p was low expressed in bladder cancer tissues and cells. circCEP128 knockdown hindered cell proliferation, migration and invasion and promoted cell apoptosis in bladder cancer. circCEP128 loss increased miR-515-5p expression through direct interaction in bladder cancer cells. MiR-515-5p depletion mitigated the influences of circCEP128 knockdown on bladder cancer cell phenotypes. SDC1 was a direct target of miR-515-5p. circCEP128 positively regulated SDC1 expression via miR-515-5p. MiR-515-5p restrained the malignant progression of bladder cancer cells by decreasing SDC1 expression. circCEP128 knockdown hindered the growth of bladder cancer xenograft tumors by up-regulating miR-515-5p and down-regulating SDC1. Conclusion: circCEP128 knockdown hampered the tumorigenesis and progression of bladder cancer by regulating miR-515-5p/SDC1 axis in vitro and in vivo, deepening our understanding on the molecular mechanisms of circCEP128 in bladder cancer.

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“…Recent years we have seen a rapid development of next generation sequencing and computational approaches, some protein non-coding RNA (ncRNA), such as micro-RNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), piwi-interacting RNA (piRNA) and small nucleolar RNA (snoRNA), which was first thought to be transcriptional noise, now have been reported to play an important role in many biological process [9][10][11][12]. Among them, miRNAs and lncRNAs, which comprise the majority of ncRNAs, were largely studied.…”

Section: Introductionmentioning

confidence: 99%

Small nucleolar RNAs signature (SNORS) identified clinical outcome and prognosis of bladder cancer (BLCA)

Cao

Yuan

et al. 2020

Cancer Cell Int

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Background: Small nucleolar RNAs (snoRNAs) are a new non-coding RNAs (ncRNAs), which have not been widely investigated and are identified to be involved in tumorigenesis. But the function of snoRNAs in BLCA has not been reported yet. Methods: SnoRNAs signature (SNORS) was constructed through LASSO cox regression analysis. Integrated analysis of candidate snoRNAs was performed to detect the correlation between copy number variation (CNV)/DNA methylation/protein/mRNA/alternative splicing (AS). Then we built a nomogram integrating independent prognostic factors to assist the clinical utility. Results: We have screened out 15 prognostic differentially expressed snoRNAs (DESs) and constructed SNORS consisting of 5 candidate snoRNAs which could appropriately stratify patients into low or high SNORS groups with distinct prognosis. Then we found 5 candidate snoRNAs might be regulated by their own CNV and DNA methylation. Moreover, 5 candidate snoRNAs were significantly correlated mRNA and alternative splicing (AS), which might regulate diverse biological process in tumorigenesis, such as "extracellular matrix", "epithelial-mesenchymal transition (EMT)", etc. signaling pathways. Furthermore, SNORS was an independent prognostic factor, which was strikingly correlated with clinical outcome. Through inporating with other variables, we have established a predictive nomogram, which was more effectively to predict prognosis than any other variables alone. Conclusion: Our findings first highlighted an important role of snoRNAs in BLCA and established a potential prognostic model which could serve as a biomarker for BLCA.

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Current Status of Functional Studies on Circular RNAs in Bladder Cancer and their Potential Role as Diagnostic and Prognostic Biomarkers: A Review

Cited by 16 publications

References 95 publications

Circ-MBOAT2 knockdown represses tumor progression and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer

Circ-MBOAT2 knockdown represses tumor progression and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer

circCEP128 Knockdown Suppresses Bladder Cancer Progression via Regulating microRNA-515-5p/SDC1 Axis

Small nucleolar RNAs signature (SNORS) identified clinical outcome and prognosis of bladder cancer (BLCA)

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