Androgen receptor suppresses vasculogenic mimicry in hepatocellular carcinoma via <i>circRNA7/miRNA7‐5p/VE‐cadherin/Notch4</i> signalling

Bao, Shixiang; Jin, Shuai; Wang, Chunhua; Tu, Peipei; Hu, Kongwang; Lü, Jing-Tao

doi:10.1111/jcmm.16022

Cited by 24 publications

(19 citation statements)

References 34 publications

(66 reference statements)

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“…Vasculogenesis mimicry (VM), a novel pattern of vascularization, is involved in HCC progression and metastasis. Androgen receptor (AR) suppressed the formation of HCC VM by downregulating circRNA7/miRNA7-5p/VE-cadherin/Notch4 signaling axis in HCC, which may be novel therapies against HCC 90 . circGFRA1 was aberrantly highly expressed in HCC tissues and cells, which may lead to poor prognosis.…”

Section: The Roles Of Circrna In Hccmentioning

confidence: 99%

The functional roles, cross-talk and clinical implications of m6A modification and circRNA in hepatocellular carcinoma

Qin¹,

Mao²,

Xue³

et al. 2021

Int. J. Biol. Sci.

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. HCC has high rates of death and recurrence, as well as very low survival rates. N6-methyladenosine (m6A) is the most abundant modification in eukaryotic RNAs, and circRNAs are a class of circular noncoding RNAs that are generated by back-splicing and they modulate multiple functions in a variety of cellular processes. Although the carcinogenesis of HCC is complex, emerging evidence has indicated that m6A modification and circRNA play vital roles in HCC development and progression. However, the underlying mechanisms governing HCC, their cross-talk, and clinical implications have not been fully elucidated. Therefore, in this paper, we elucidated the biological functions and molecular mechanisms of m6A modification in the carcinogenesis of HCC by illustrating three different regulatory factors ("writer", "eraser", and "reader") of the m6A modification process. Additionally, we dissected the functional roles of circRNAs in various malignant behaviors of HCC, thereby contributing to HCC initiation, progression and relapse. Furthermore, we demonstrated the cross-talk and interplay between m6A modification and circRNA by revealing the effects of the collaboration of circRNA and m6A modification on HCC progression. Finally, we proposed the clinical potential and implications of m6A modifiers and circRNAs as diagnostic biomarkers and therapeutic targets for HCC diagnosis, treatment and prognosis evaluation.

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Section: The Roles Of Circrna In Hccmentioning

confidence: 99%

The functional roles, cross-talk and clinical implications of m6A modification and circRNA in hepatocellular carcinoma

Qin¹,

Mao²,

Xue³

et al. 2021

Int. J. Biol. Sci.

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“…As miR-7 targets Notch3, its downregulation leads to Notch signaling activation in the same type of cancer cells [ 157 ]. Besides Notch3, Notch4 and VE cadherin were also found to be miR-7 targets [ 107 ]. miR-7 also downregulates VDAC1 in hepatocellular carcinoma and influences proliferation and migration [ 118 ], as well as the fibroblast growth factor receptor FGFR4, a key molecule for liver protection from chronic injury.…”

Section: Mir-7 Role In Gastrointestinal Tumoursmentioning

confidence: 99%

MiR-7 in Cancer Development

2021

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MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the fine-tuning of several signaling pathways, acting mainly as tumor suppressor. Through downregulation of PI3K and MAPK pathways, its dominant role is the suppression of proliferation and survival, stimulation of apoptosis and inhibition of migration. Besides these functions, it has numerous additional roles in the differentiation process of different cell types, protection from stress and chromatin remodulation. One of the most investigated tissues is the brain, where its downregulation is linked with glioblastoma cell proliferation. Its deregulation is found also in other tumor types, such as in liver, lung and pancreas. In some types of lung and oral carcinoma, it can act as oncomir. miR-7 roles in cell fate determination and maintenance of cell homeostasis are still to be discovered, as well as the possibilities of its use as a specific biotherapeutic.

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“…73 A total of eight miRNAs, including miR-7, miR-34a, miR-34c, miR-96, miR-183, miR-181c, miR-302 and miR-1179, were found to target Notch4 and inhibit its expression in cancer cells (Table 3). 47,51,71,[74][75][76][77] However, their expression levels are aberrantly downregulated in tumor tissues, which is partly caused by hypermethylation of their gene promoters, or overexpression of the upstream circRNA. 51,71,76 MiRNA mimics, DNA demethylation inducers or circRNA inhibitors can recover the expression of Notch4-targeted miRNAs in cancer cells, thereby reducing Notch4 expression and inhibiting tumor progression.…”

Section: Inhibiting Notch4 Expression and Activationmentioning

confidence: 99%

“… 30 , 70 Recently, the oncogenic circular RNA 7 was found to inhibit miR-7-5p expression in HCC, activating Notch4 expression and thus promoting VM formation. 71 Suppressing the expression of circRNA 7 or Notch4, as well as recovering miR-7-5p expression, could effectively block VM in HCC. 71 In aggressive melanoma, VM formation induced by Notch4 activity is dependent on the expression of Nodal and VE-cadherin.…”

Section: Notch4 In Tumor Vasculaturementioning

confidence: 99%

“… 71 Suppressing the expression of circRNA 7 or Notch4, as well as recovering miR-7-5p expression, could effectively block VM in HCC. 71 In aggressive melanoma, VM formation induced by Notch4 activity is dependent on the expression of Nodal and VE-cadherin. Accordingly, blocking Nodal/VE-cadherin signaling may be a potential strategy for inhibiting Notch4-induced VM formation in melanoma.…”

Section: Notch4 In Tumor Vasculaturementioning

confidence: 99%

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Targeting Notch4 in Cancer: Molecular Mechanisms and Therapeutic Perspectives

Xiu¹,

Zeng²,

Shan³

et al. 2021

CMAR

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The dysregulation of Notch signaling is found in many cancers and is closely related to cancer progression. As an important Notch receptor, abnormal Notch4 expression affects several tumor-cell behaviors, including stemness, the epithelial-mesenchymal transition, radio/chemoresistance and angiogenesis. In order to inhibit the oncogenic effects of Notch4 activation, several methods for targeting Notch4 signaling have been proposed. In this review, we summarize the known molecular mechanisms through which Notch4 affects cancer progression. Finally, we discuss potential Notch4-targeting therapeutic strategies as a reference for future research.

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Androgen receptor suppresses vasculogenic mimicry in hepatocellular carcinoma via circRNA7/miRNA7‐5p/VE‐cadherin/Notch4 signalling

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 24 publications

References 34 publications

The functional roles, cross-talk and clinical implications of m6A modification and circRNA in hepatocellular carcinoma

The functional roles, cross-talk and clinical implications of m6A modification and circRNA in hepatocellular carcinoma

MiR-7 in Cancer Development

Targeting Notch4 in Cancer: Molecular Mechanisms and Therapeutic Perspectives

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