Downregulated hsa_circ_0077837 and hsa_circ_0004826, facilitate bladder cancer progression and predict poor prognosis for bladder cancer patients

Shen, Chong; Wu, Zhouliang; Wang, Yujie; Gao, Shen; Da, La; Xie, Linguo; Qie, Yunkai; Tian, Dan; Hu, Hailong

doi:10.1002/cam4.3006

Cited by 34 publications

(27 citation statements)

References 65 publications

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“…Of them, through dual-luciferase reporter assay, hsa_circ_0026782 has been verified that it directly targets miR-874. In accordance with these results, Shen et al (2020) also reported that miR-874-3p was the predicted MREs for hsa_circ_0026782, which confirms the accuracy of our results. In addition, several miRNAs in ceRNA network were reported previously to be involved in the cell cycle, angiogenesis, mucosal fibrosis, and so on.…”

Section: Discussionsupporting

confidence: 92%

Construction of circRNA-miRNA-mRNA Network for Exploring Underlying Mechanisms of Lubrication Disorder

Cong

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Lubrication disorder is a common health issue that manifests as insufficient sexual arousal at the beginning of sex. It often causes physical and psychological distress. However, there are few studies on lubrication disorder, and the complexity of circular RNA (circRNA) and the related competing endogenous RNA (ceRNA) network in lubrication disorder is still poorly known. Therefore, this study aims to build a regulatory circRNA-micro (mi)RNA-mRNA network and explore potential molecular markers of lubrication disorder. In the study, 12 subjects were recruited, including 6 in the lubrication disorder group and 6 in the normal control group. RNA sequencing was exploited to identify the expression profiles of circRNA, miRNA and mRNA between two groups, and then to construct the circRNA-miRNA-mRNA networks. The enrichment analyses of the differentially expressed (DE)-mRNAs were examined via Gene Set Enrichment Analysis (GSEA). Furthermore, the expression level and interactions among circRNA, miRNA, and mRNA were validated using real-time quantitative polymerase chain reaction (RT-qPCR) and dual-luciferase reporter assays. In the results, 73 circRNAs, 287 miRNAs, and 354 target mRNAs were differentially expressed between two groups when taking | Log2 (fold change)| > 1 and P-value < 0.05 as criteria, and then the results of GSEA revealed that DE-mRNAs were linked with “vascular smooth muscle contraction,” “aldosterone regulated sodium reabsorption,” “calcium signaling pathway,” etc. 19 target relationships among 5 circRNAs, 4 miRNAs, and 7 mRNAs were found and constructed the ceRNA network. Among them, hsa-miR-212-5p and hsa-miR-874-3p were demonstrated to be related to the occurrence of lubrication disorder. Eventually, consistent with sequencing, RT-qPCR showed that hsa_circ_0026782 and ASB2 were upregulated while hsa-miR-874-3p was downregulated, and dual-luciferase reporter assays confirmed the interactions among them. In summary, the findings indicate that the circRNA-miRNA-mRNA regulatory network is presented in lubrication disorder, and ulteriorly provide a deeper understanding of the specific regulatory mechanism of lubrication disorder from the perspective of the circRNA-miRNA-mRNA network.

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Section: Discussionsupporting

confidence: 92%

Construction of circRNA-miRNA-mRNA Network for Exploring Underlying Mechanisms of Lubrication Disorder

Cong

Zhang

et al. 2021

Front. Cell Dev. Biol.

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“…CircEPB41L2 has been previously reported to be down-regulated in human lung adenocarcinoma and bladder cancer, and could predict poor prognosis for patients. 24 , 25 In this study, we also found that the downregulation of circEPB41L2 expression in HCC tissues could promote cell proliferation and metastasis, and thus was significantly correlated with worse RFS time and OS time for HCC patients. Taken together, those results suggested that circEPB41L2 might function as a suppressor role in many solid tumors, including HCC.…”

Section: Discussionsupporting

confidence: 57%

Circular RNA CircEPB41L2 Functions as Tumor Suppressor in Hepatocellular Carcinoma Through Sponging miR-590-5p

Chen¹,

He²,

Qiu³

et al. 2021

CMAR

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Background: Circular RNAs (circRNAs) could interact with miRNAs to regulate gene expression, participating in hepatocellular carcinoma (HCC) initiation and development. This work aimed to determine the potential function and molecular mechanism of circEPB41L2 (hsa_circ_0077837) during HCC progression. Materials and Methods: The expression of circEPB41L2 in HCC tissues and HCC cell lines was quantified using real-time quantitative PCR (qRT-PCR). CCK-8 assays and colony formation assays were utilized to detect the proliferation of HCC cells. Wound healing assay and transwell assay were performed to determine the capability of migration and invasion for HCC cells. Western blot was conducted to determine gene expression on protein levels. The effect of circEPB41L2 on HCC in vivo was investigated via xenograft experiment. Interaction between circEPB41L2 and miR-590-5p was predicted through bioinformatics methods and confirmed via luciferase reporter assay. Results: Extensive analysis of circRNA profiles in tumor and matched para-tumor tissues collected from 61 HCC patients identified that circEPB41L2 was significantly downregulated in HCC, which was further confirmed in another HCC group by qRT-PCR analysis. The clinicopathological analysis revealed that down-regulation of circEPB41L2 was negatively associated with tumor size, vascular invasion and alpha-fetoprotein, while positively correlated with HCC prognosis. The biological function experiments showed that overexpression of circEPB41L2 could obviously inhibit the proliferation and metastasis of HCC cells in vitro, while knockdown of circEPB41L2 induced opposite results. Moreover, we also found that circEPB41L2 inhibited HCC migration and invasion though EMT signaling pathway. Similarly, overexpression of circEPB41L2 can also significantly inhibit the proliferation of HCC cells in vivo. Bioinformatic analysis and luciferase reporter assay revealed that circEPB41L2 interacts directly with miR-590-5p and the corresponding biological functions were also verified in miRNA rescue experiments. Conclusion:Our results suggest that circEPB41L2 might function as a tumor suppressor during HCC progression by sponging miR-590-5p.

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“…In addition, patients with ccRCC and a high level of circ_0085576 had a poor OS and DFS rate; circ_0085576 is derived from the ArfGAP with SH3 domain ankyrin repeat and PH domain 1 gene ( 67 ). By contrast, circ_0004826 and circ_0077837, which are spliced from the utrophin and erythrocyte membrane protein band 4.1-like 2 genes, respectively, are usually expressed at a low level in BC, inhibit tumor cell development and act as a biomarker for OS and RFS in patients with BC ( Table II ) ( 68 ). circRNAs can also act as biomarkers for the effect of drug treatment.…”

Section: Circrnas Act As Biomarkers For the Diagnosis And Prognosis Omentioning

confidence: 99%

Functions of circular RNAs in bladder, prostate and renal cell cancer (Review)

Yang

Zou

et al. 2021

Mol Med Rep

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Circular RNAs (circRNAs) are a class of non-coding RNAs formed by covalently closed loops through back-splicing and exon-skipping. circRNAs have been confirmed to play a vital role in various biological functions, acting as microRNA sponges and reservoirs, as well as combining with RNA-binding proteins during the progression of multiple cancer types. Therefore, the present review evaluated recent research articles in PubMed that were published between November 2017 and September 2020. Key word search strings included: ‘Circular RNA (circRNA) AND bladder cancer (BC)’, ‘circular RNA (circRNA) AND prostate cancer (PCa)’ and ‘circular RNA (circRNA) AND renal cell cancer (RCC)’. In total, >58 circRNAs were found to be implicated in urological cancers, with several of the circRNAs targeting common carcinogenic pathways, such as the AKT, TGF-β, MAPK, VEGF and even metabolic pathways. circRNAs are important modulators of BC, PCa and RCC. circRNAs are functionally implicated in the pathogenesis of these cancer types, and have been found to act as biomarkers for the diagnosis and prognosis of urological cancer. However, to the best of our knowledge, the functions of circRNAs in tumors of the urinary system remain largely unknown and require further research.

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Downregulated hsa_circ_0077837 and hsa_circ_0004826, facilitate bladder cancer progression and predict poor prognosis for bladder cancer patients

Cited by 34 publications

References 65 publications

Construction of circRNA-miRNA-mRNA Network for Exploring Underlying Mechanisms of Lubrication Disorder

Construction of circRNA-miRNA-mRNA Network for Exploring Underlying Mechanisms of Lubrication Disorder

Circular RNA CircEPB41L2 Functions as Tumor Suppressor in Hepatocellular Carcinoma Through Sponging miR-590-5p

Functions of circular RNAs in bladder, prostate and renal cell cancer (Review)

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