Epithelial mesenchymal transition Transcription Factor (TF): The structure, function and microRNA feedback loop

Alidadiani, Neda; Ghaderi, Shahrooz; Dilaver, Nafi; Bakhshamin, Saina; Bayat, Mansour

doi:10.1016/j.gene.2018.06.049

Cited by 32 publications

(23 citation statements)

References 62 publications

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“…Understanding of the dynamic properties of regulatory networks involved in the metastatic progression is crucial towards the improvement of the clinical outcome of ovarian cancer. The tumor aggressiveness is regulated by the complex changes in EMT-associated cell phenotypes, critically mediated by the EMT-TF as reflected by their association with poor clinical outcome in many tumors 41 . The many signaling cues that activate EMT-TF increase the complexity of the turning on of EMT program in tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Targeting endothelin 1 receptor-miR-200b/c-ZEB1 circuitry blunts metastatic progression in ovarian cancer

et al. 2020

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Identification of regulatory mechanisms underlying the poor prognosis of ovarian cancer is necessary for diagnostic and therapeutic implications. Here we show that endothelin A receptor (ETAR) and ZEB1 expression is upregulated in mesenchymal ovarian cancer and correlates with poor prognosis. Notably, the expression of ETAR and ZEB1 negatively correlates with miR-200b/c. These miRNAs, besides targeting ZEB1, impair ETAR expression through the 3’UTR binding. ZEB1, in turn, restores ETAR levels by transcriptionally repressing miR-200b/c. Activation of ETAR drives the expression of ZEB1 integrating the miR-200/ZEB1 double negative feedback loop. The ETAR-miR-200b/c-ZEB1 circuit promotes epithelial-mesenchymal transition, cell plasticity, invasiveness and metastasis. Of therapeutic interest, ETAR blockade with macitentan, a dual ETAR and ETBR antagonist, increases miR-200b/c and reduces ZEB1 expression with the concomitant inhibition of metastatic dissemination. Collectively, these findings highlight the reciprocal network that integrates ETAR and ZEB1 axes with the miR-200b/c regulatory circuit to favour metastatic progression in ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Targeting endothelin 1 receptor-miR-200b/c-ZEB1 circuitry blunts metastatic progression in ovarian cancer

et al. 2020

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“…3b ), several of which accompanied with identified miRNAs up-regulation (including miR-181a-5p-5p, miR-29b-3p and miR-30e 66 – 68 ). The unexpected changes of these genes suggest complicated mechanisms on TF-miR interaction, which might provide a feedback or feedforward loop and cross-gene regulation consequently 69 . Further research is required to uncover the potential molecular mechanisms of TF-miRNA interaction on tumor EMT switching in OSCC.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-transcription factor network analysis reveals miRNAs cooperatively suppress RORA in oral squamous cell carcinoma

Zheng

Wu²,

Liao³

et al. 2018

Oncogenesis

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Oral squamous cell carcinoma (OSCC) represents over 90% of oral cancer incidence, while its mechanisms of tumorigenesis remain poorly characterized. In this study, we applied RNA-seq and microRNA-seq methodologies in four pairs of cancer and adjacent normal tissues to profile the contribution of miRNAs to tumorigenesis-altered functional pathways by constructing a comprehensive miRNA-mediated mRNA regulatory network. There were 213 differentially expressed (DE) miRNAs and 2172 DE mRNAs with the involvement of negative miRNA-mRNA interactions identified by at least two pairs of cancerous tissues. GO analysis revealed that the upregulated microRNAs significantly contributed to a global down-regulation of a number of transcription factors (TFs) in OSCC. Among the negative regulatory networks between the selected miRNAs (133) and TFs (167), circadian rhythm genes (RORA, RORB, RORC, and CLOCK) simultaneously regulated by multiple microRNAs were of particular interest. For instance, RORA transcript was predicted to be targeted by 25 co-upregulated miRNAs, of which, miR-503-5p, miR-450b-5p, miR-27a-3p, miR-181a-5p and miR-183-5p were further validated to directly target RORA, resulting in a stronger effect on RORA suppression together. In addition, we showed that the mRNA and protein expression levels of RORα were significantly decreased in most OSCC samples, associated with advanced clinical stage and poor prognosis. RORα significantly suppressed the proliferation of OSCC cells in vitro and in vivo. Attenuated RORα decreased p53 protein expression and suppressed p53 phosphorylation activity. Altogether, our results strongly suggest the importance of the role of miRNAs in regulating the activity of circadian rhythm-related TFs network during OSCC tumorigenesis, and provide further clues to understand the clinical link between circadian rhythm and cancer therapy.

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“…SNAIL plays a role in many physiological and pathological processes, such as chronic inflammation, fibrosis, EMT induction, the regulation of cancer stem cells, the control of cell metabolism, the suppression of estrogen receptor signaling, and in particular the development and metastasis of tumors [3]. Currently, many research papers focus not only on interaction between SNAIL and different genes, but also on the interplay between SNAIL and non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs [20]. In this review, we discuss recent advances in those fields.…”

Section: Different Pathways Regulated By Snailmentioning

confidence: 99%

Interplay among SNAIL Transcription Factor, MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Regulation of Tumor Growth and Metastasis

Skrzypek

Majka

2020

Cancers

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SNAIL (SNAI1) is a zinc finger transcription factor that binds to E-box sequences and regulates the expression of genes. It usually acts as a gene repressor, but it may also activate the expression of genes. SNAIL plays a key role in the regulation of epithelial to mesenchymal transition, which is the main mechanism responsible for the progression and metastasis of epithelial tumors. Nevertheless, it also regulates different processes that are responsible for tumor growth, such as the activity of cancer stem cells, the control of cell metabolism, and the regulation of differentiation. Different proteins and microRNAs may regulate the SNAIL level, and SNAIL may be an important regulator of microRNA expression as well. The interplay among SNAIL, microRNAs, long non-coding RNAs, and circular RNAs is a key event in the regulation of tumor growth and metastasis. This review for the first time discusses different types of regulation between SNAIL and non-coding RNAs with a focus on feedback loops and the role of competitive RNA. Understanding these mechanisms may help develop novel therapeutic strategies against cancer based on microRNAs.

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Epithelial mesenchymal transition Transcription Factor (TF): The structure, function and microRNA feedback loop

Cited by 32 publications

References 62 publications

Targeting endothelin 1 receptor-miR-200b/c-ZEB1 circuitry blunts metastatic progression in ovarian cancer

Targeting endothelin 1 receptor-miR-200b/c-ZEB1 circuitry blunts metastatic progression in ovarian cancer

MicroRNA-transcription factor network analysis reveals miRNAs cooperatively suppress RORA in oral squamous cell carcinoma

Interplay among SNAIL Transcription Factor, MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Regulation of Tumor Growth and Metastasis

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