ZEB1-Mediated Transcriptional Upregulation of circWWC3 Promotes Breast Cancer Progression through Activating Ras Signaling Pathway

Meng, Lingjiao; Liu, Sihua; Liu, Fei; Sang, Meijie; Ju, Yingchao; Fan, Xinyan; Gu, Lina; Li, Ziyi; Chen, Geng; Sang, Meixiang

doi:10.1016/j.omtn.2020.08.015

Cited by 33 publications

(36 citation statements)

References 55 publications

(61 reference statements)

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“…Meng et al discovered a novel WWC3-related tumor-promoting mechanism that involved the zinc finger E-box binding homeobox 1 (ZEB1), an important driver of tumor growth and metastasis in BC. ZEB1 induces the synthesis of a circular RNA (cirRNA) derived from the WWC3 gene locus, circWWC3 [ 58 ]. An enhanced circWWC3 level, associated with poor prognosis in BC, alters the miRNA expression pattern and subsequently activates the oncogenic Ras signal pathway in BC.…”

Section: Wwc Proteins and Cancermentioning

confidence: 99%

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WWC Proteins: Important Regulators of Hippo Signaling in Cancer

Höffken

Hermann

Pavenstädt

et al. 2021

Cancers

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The Hippo signaling pathway is known to regulate cell differentiation, proliferation and apoptosis. Whereas activation of the Hippo signaling pathway leads to phosphorylation and cytoplasmic retention of the transcriptional coactivator YAP, decreased Hippo signaling results in nuclear import of YAP and subsequent transcription of pro-proliferative genes. Hence, a dynamic and precise regulation of the Hippo signaling pathway is crucial for organ size control and the prevention of tumor formation. The transcriptional activity of YAP is controlled by a growing number of upstream regulators including the family of WWC proteins. WWC1, WWC2 and WWC3 represent cytosolic scaffolding proteins involved in intracellular transport processes and different signal transduction pathways. Earlier in vitro experiments demonstrated that WWC proteins positively regulate the Hippo pathway via the activation of large tumor suppressor kinases 1/2 (LATS1/2) kinases and the subsequent cytoplasmic accumulation of phosphorylated YAP. Later, reduced WWC expression and subsequent high YAP activity were shown to correlate with the progression of human cancer in different organs. Although the function of WWC proteins as upstream regulators of Hippo signaling was confirmed in various studies, their important role as tumor modulators is often overlooked. This review has been designed to provide an update on the published data linking WWC1, WWC2 and WWC3 to cancer, with a focus on Hippo pathway-dependent mechanisms.

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Section: Wwc Proteins and Cancermentioning

confidence: 99%

“…An enhanced circWWC3 level, associated with poor prognosis in BC, alters the miRNA expression pattern and subsequently activates the oncogenic Ras signal pathway in BC. Silencing of circWWC3 significantly suppresses the proliferation, migration and invasion of BC cells [ 58 ].…”

Section: Wwc Proteins and Cancermentioning

confidence: 99%

WWC Proteins: Important Regulators of Hippo Signaling in Cancer

Höffken

Hermann

Pavenstädt

et al. 2021

Cancers

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“…CircWWC3: Zinc finger E-box binding homeobox 1 (ZEB1) is a transcription factor and an important driver of BC progression [ 68 ]. Meng et al attempted to identify ZEB1-regulated circRNAs in BC [ 69 ]. CircWWC3 was one out of 15 identified circRNAs found to be upregulated following ZEB1 transfection in a TNBC cell line using a circRNA microarray [ 69 ].…”

Section: Function Of Circrnas In Breast Cancermentioning

confidence: 99%

“…Meng et al attempted to identify ZEB1-regulated circRNAs in BC [ 69 ]. CircWWC3 was one out of 15 identified circRNAs found to be upregulated following ZEB1 transfection in a TNBC cell line using a circRNA microarray [ 69 ]. ZEB1 was found to upregulate circWWC3 expression but not the linear WWC3 mRNA expression [ 69 ].…”

Section: Function Of Circrnas In Breast Cancermentioning

confidence: 99%

“…CircWWC3 was one out of 15 identified circRNAs found to be upregulated following ZEB1 transfection in a TNBC cell line using a circRNA microarray [ 69 ]. ZEB1 was found to upregulate circWWC3 expression but not the linear WWC3 mRNA expression [ 69 ]. WWC3 is a tumor suppressor that is downregulated in cancer and low WWC3 expression is associated with poor prognosis of cancer patients [ 70 ].…”

Section: Function Of Circrnas In Breast Cancermentioning

confidence: 99%

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Circular RNAs: Potential Applications as Therapeutic Targets and Biomarkers in Breast Cancer

Sarkar

Diermeier

2021

ncRNA

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Circular RNAs (circRNAs) are a class of non-coding RNAs that form a covalently closed loop. A number of functions and mechanisms of action for circRNAs have been reported, including as miRNA sponge, exerting transcriptional and translational regulation, interacting with proteins, and coding for peptides. CircRNA dysregulation has also been implicated in many cancers, such as breast cancer. Their relatively high stability and presence in bodily fluids makes cancer-associated circRNAs promising candidates as a new biomarker. In this review, we summarize the research undertaken on circRNAs associated with breast cancer, discuss circRNAs as biomarkers, and present circRNA-based therapeutic approaches.

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The transcription factor ZEB1 mediates the progression of epithelial ovarian cancer by promoting the transcription of CircANKRD17

Cai

Zhang

2022

J Biochem & Molecular Tox

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Zinc finger E‐box‐binding homeobox 1 (ZEB1) is a key transcription factor that regulates the process of epithelial‐mesenchymal transition (EMT) in various tumors. However, its role in epithelial ovarian cancer (EOC) is far from understood. The present study aimed to explore the role and potential mechanism of action of ZEB1 in EOC. A quantitative reverse transcription‐polymerase chain reaction was used to detect ZEB1 expression levels. The Cell Counting Kit‐8 assay, transwell assays, and flow cytometry were used to verify the effects of ZEB1 on the proliferation, invasion, migration, apoptosis, and EMT of EOC, respectively. RNA sequencing identified the effect of knocking down ZEB1 on circular RNAs in EOC cells. Dual‐luciferase activity assay and chromatin immunoprecipitation experiments were used to verify the regulatory effect of ZEB1 on the circular RNA ANKRD17 (CircANKRD17; ID: hsa_circ_0007883) at the transcriptional level. Higher ZEB1 expression was found in EOC tissues and cells and was closely related to tumor metastasis, advanced stages, and lower survival rates. Furthermore, silencing ZEB1 inhibited the proliferation, invasion, migration, and EMT of EOC cells but enhanced cell apoptosis. Mechanistically, knockdown of ZEB1 resulted in the greatest downregulation of CircANKRD17 in EOC cells, and ZEB1 significantly promoted the expression of CircANKRD17 and had no significant effect on ANKRD17 messenger RNA expression. Further experiments verified that ZEB1 mediates the regulation of EOC processes by CircANKRD17. Highly expressed ZEB1 promoted proliferation, invasion, migration, and EMT while it inhibited cell apoptosis in EOC by promoting the transcription of CircANKRD17, providing a potential target for the treatment of EOC.

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ZEB1-Mediated Transcriptional Upregulation of circWWC3 Promotes Breast Cancer Progression through Activating Ras Signaling Pathway

Cited by 33 publications

References 55 publications

WWC Proteins: Important Regulators of Hippo Signaling in Cancer

WWC Proteins: Important Regulators of Hippo Signaling in Cancer

Circular RNAs: Potential Applications as Therapeutic Targets and Biomarkers in Breast Cancer

The transcription factor ZEB1 mediates the progression of epithelial ovarian cancer by promoting the transcription of CircANKRD17

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