CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression

Chen, Luping; Shi, Juan; Wu, Yalong; Qiu, Ronglin; Zeng, Lexiang; Lou, Lei; Su, Jianhang; Liao, Minyi; Deng, Xiaogeng

doi:10.18632/aging.103748

Cited by 33 publications

(16 citation statements)

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“…In addition, hsa_cric_0000594 has been confirmed and acts as a sponger for miR-217 to facilitate cell growth and metastasis in HB ( Song et al, 2019b ). And circCDR1as accelerates proliferation and stemness in HB via regulating miR-7-5p/KLF4 axis ( Chen et al, 2020 ). CircHMGCS1 also has been demonstrated increasing in HB to induce proliferation and glutaminolysis by miR-503-5p/IGF-PI3K-AKT axis ( Zhen et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…CircRNA_104718 has been found that promotes hepatocellular carcinoma (HCC) progression by regulating miR-218-5p/TXNDC5 signaling pathway ( Yu et al, 2019 ). Furthermore, abundant researches indicate that circRNAs emerge the dominant roles in regulation of tumorigenesis, metastasis, and recurrence in HB ( Zhen et al, 2019 ; Chen et al, 2020 ). However, the role of circSETD3 and its regulatory effects in HB remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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RETRACTED: CircSETD3 (Hsa_circ_0000567) Suppresses Hepatoblastoma Pathogenesis via Targeting the miR-423-3p/Bcl-2-Interacting Mediator of Cell Death Axis

Li¹,

Wang²,

Liu³

et al. 2021

Front. Genet.

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Background: Up until now, the role of circSETD3 (Has_circ_0000567) in regulating cancer development has been reported in several tumors, but the role and regulatory mechanism of circSETD3 in hepatoblastoma (HB) remain unclear.Methods: The qPCR and western blotting were used to determine the mRNA and protein levels in the present study. Stability of circular RNA was detected by RNA digested experiments. The gain-of-function and rescue experiments were used to explore the function and mechanism of circSETD3 in HB. Cell counting kit-8, colony formation, transwell assay, and xenograft mice model were used to detect effects and regulatory mechanism of circSETD3/miR-423-3p/Bim axis on cell aggressive phenotype in vitro and in vivo.Results: Here, we identified that circSETD3 downregulated in both HB clinical tissues and cell lines, compared to that of normal tissues and cells. Further gain-of-function experiments validated that circSETD3 overexpression inhibited cell proliferation, viability, migration, epithelial-mesenchymal transition (EMT) and tumorigenesis, and induced cell apoptosis in HB cells. Next, we validated that miR-423-3p targeted both circSETD3 and 3′ untranslated region (3′UTR) of Bim, and circSETD3 positively regulated Bim in HB cells through sponging miR-423-3p in a competing endogenous RNA (ceRNA)-dependent manner. Furthermore, through conducting reversal experiments, we evidenced that the inhibiting effects of circSETD3 overexpression on HB development were abrogated by upregulating miR-423-3p and downregulating Bim.Conclusion: Taken together, we evidenced that circSETD3 sponged miR-423-3p to upregulate Bim, resulting in the inhibition of HB development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RETRACTED: CircSETD3 (Hsa_circ_0000567) Suppresses Hepatoblastoma Pathogenesis via Targeting the miR-423-3p/Bcl-2-Interacting Mediator of Cell Death Axis

Li¹,

Wang²,

Liu³

et al. 2021

Front. Genet.

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“…The activation of this pathway enhances the expression of the enzyme glutamine synthetase (GLS), which is also upregulated in HB tissues, thereby inducing the production of glutamine [169] . Glutamine metabolism favors tumor growth and adaptation, representing a crucial event in cancer growth [205] . According to this, circHMGCS1 knockdown abrogates cell proliferation and induces apoptosis, accompanied by downregulation of the AKT pathway and a decline in GLS mRNA levels in HuH6 and HepG2 HB cells.…”

Section: Circular Rnas In Hbmentioning

confidence: 99%

Epigenetics in hepatoblastoma

Clavería-Cabello¹,

Arechederra²,

Berasain³

et al. 2021

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Hepatoblastoma (HB) is the most frequent pediatric primary liver tumor. When the tumoral lesions can be resected, prognosis is generally favorable. However, there is a significant number of cases in which resection is not possible at diagnosis, and patients usually receive neo-adjuvant cisplatin-based chemotherapy prior to surgery. Unfortunately, some HBs develop resistance to initial chemotherapy or after recurrence, progressing to metastatic disease. Moreover, long-term side effects of chemotherapy remain a serious concern. Understanding the molecular bases of HB development and progression is thus essential for the identification of more efficacious therapies. HBs have a very low mutational burden, and the most frequent mutations occur in the CTNN1B gene (> 80% of cases) and to a lesser extent in NFE2L2 (~10% of cases). These observations suggest that other pathogenic processes besides genetic mutations may play a role in HB tumorigenesis. Epigenetic mechanisms encompass a variety of molecular processes with a tremendous potential to regulate gene expression. They include the covalent modifications of DNA and histones, the activity of enzymatic chromatin remodelers, and the expression of noncoding RNAs. Dysregulation of epigenetic processes has clearly become a hallmark of cancer. Regarding HB, recent studies have explored its epigenetic landscape, the expression of specific epigenetic effectors, and the tumorigenic consequences of epigenetic alterations. The reversible nature of most epigenetic modifications and the possibility to target non-coding RNAs may pave the way for new therapeutic avenues in HB. Here, we summarize and discuss the most relevant findings in this less explored aspect of HB.

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“…Recently, four research groups have analyzed the expression of CDR1as in HCC and its relationship with prognosis ( 40 – 43 ) ( Table 1 ). Although the expression of CDR1as in HCC tissues remains controversial, upregulation of CDR1as is an independent risk factor for hepatic microvascular invasion (MVI) and promotes the proliferation and invasion of HCC cells by inhibiting the expression of mir-7 and its downstream target genes CCNE1 , PIK3CD , KLF4 , and p70S6K ( Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

The Prognostic and Predictive Significance of circRNA CDR1as in Tumor Progression

Fang

Yangyang

et al. 2021

Front. Oncol.

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Cerebellar degeneration-related protein 1 antisense (CDR1as) is an important member of the circRNAs family, also known as cirs-7. Its main function in vivo is to act as a mir-7 sponge. Accumulated studies show that CDR1as is closely related to various diseases, especially cancer. Our analysis show that CDR1as expression in human cancer is significantly associated with poor overall survival (hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 2.06–3.04; p < 0.00001) and that high CDR1as expression is associated with the tumor node metastasis stage (odds ratio [OR] = 2.13, 95% CI = 1.63–2.78; p < 0.00001), and distant metastasis (OR = 3.50, 95% CI = 1.90–6.64; p < 0.00001). Furthermore, the results reveal the prognostic significance of CDR1as in neoplasms of the digestive system (HR = 1.69, 95% CI = 2.14–2.71; p < 0.001), colorectal cancer (HR = 1.34, 95% CI = 1.96–2.85; p < 0.001), and non-small cell lung cancer (HR = 2.40, 95% CI = 3.42–4.83; p = 0.008). In this study, we summarize in detail the latest research findings and demonstrate the function and regulatory mechanism of CDR1as in various cancer processes, and its potential as a biomarker for cancer prevention and prognosis.

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CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression

Cited by 33 publications

References 0 publications

RETRACTED: CircSETD3 (Hsa_circ_0000567) Suppresses Hepatoblastoma Pathogenesis via Targeting the miR-423-3p/Bcl-2-Interacting Mediator of Cell Death Axis

RETRACTED: CircSETD3 (Hsa_circ_0000567) Suppresses Hepatoblastoma Pathogenesis via Targeting the miR-423-3p/Bcl-2-Interacting Mediator of Cell Death Axis

Epigenetics in hepatoblastoma

The Prognostic and Predictive Significance of circRNA CDR1as in Tumor Progression

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