EMT signaling: potential contribution of CRISPR/Cas gene editing

Mohammadinejad, Reza; Biagioni, Alessio; Arunkumar, Ganesan; Shapiro, Rebecca; Chang, Kun-Che; Sedeeq, Mohammed; Taiyab, Aftab; Hashemabadi, Mohammad; Pardakhty, Abbas; Thiery, Jean Paul; Aref, Amir Reza; Azimi, Iman

doi:10.1007/s00018-020-03449-3

Cited by 23 publications

(21 citation statements)

References 235 publications

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“…Epithelial cells have cell-cell junctions, apico-basal polarity and low potential in migration. The epithelial cells are detected via their cell surface markers including E cadherin (as the most important and well-known factor), cytokeratins, occluding and claudins [ 40 , 41 , 42 , 43 ]. However, these properties are reversed in mesenchymal cells during EMT.…”

Section: Emt Mechanismmentioning

confidence: 99%

Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer

et al. 2020

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Bladder cancer (BC) is the 11th most common diagnosed cancer, and a number of factors including environmental and genetic ones participate in BC development. Metastasis of BC cells into neighboring and distant tissues significantly reduces overall survival of patients with this life-threatening disorder. Recently, studies have focused on revealing molecular pathways involved in metastasis of BC cells, and in this review, we focus on microRNAs (miRNAs) and their regulatory effect on epithelial-to-mesenchymal transition (EMT) mechanisms that can regulate metastasis. EMT is a vital process for migration of BC cells, and inhibition of this mechanism restricts invasion of BC cells. MiRNAs are endogenous non-coding RNAs with 19–24 nucleotides capable of regulating different cellular events, and EMT is one of them. In BC cells, miRNAs are able to both induce and/or inhibit EMT. For regulation of EMT, miRNAs affect different molecular pathways such as transforming growth factor-beta (TGF-β), Snail, Slug, ZEB1/2, CD44, NSBP1, which are, discussed in detail this review. Besides, miRNA/EMT axis can also be regulated by upstream mediators such as lncRNAs, circRNAs and targeted by diverse anti-tumor agents. These topics are also discussed here to reveal diverse molecular pathways involved in migration of BC cells and strategies to target them to develop effective therapeutics.

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Section: Emt Mechanismmentioning

confidence: 99%

Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer

et al. 2020

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“…[35][36][37] Moreover, to intricate an already debated and complex process, cancer cells are often reported to display different degrees of EMT phenotypes. [38][39][40][41] As reported above, SNHGs exert multiple roles being able to act as molecular sponges for several miRNAs (Figure 2) or binding proteins modulating in that way multiple biological processes, including the EMT in cancer. 28 The known SNHGs in EMT are resumed in Table 2.…”

Section: Small Nucleolar Rna Host Genes In Emt Processmentioning

confidence: 84%

“…Indeed, EMT‐induced cells demonstrate enhanced migration, invasion, and frequently express N‐cadherin at the expense of E‐cadherin reducing in this way the intercellular adhesion 35–37 . Moreover, to intricate an already debated and complex process, cancer cells are often reported to display different degrees of EMT phenotypes 38–41 …”

Section: Small Nucleolar Rna Host Genes In Emt Processmentioning

confidence: 99%

Small nucleolar RNA host genes promoting epithelial–mesenchymal transition lead cancer progression and metastasis

Biagioni¹,

Tavakol

Ahmadirad

et al. 2021

IUBMB Life

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The small nucleolar RNA host genes (SNHGs) belong to the long non-coding RNAs and are reported to be able to influence all three levels of cellular information-bearing molecules, that is, DNA, RNA, and proteins, resulting in the generation of complex phenomena. As the host genes of the small nucleolar RNAs (snoRNAs), they are commonly localized in the nucleolus, where they exert multiple regulatory functions orchestrating cellular homeostasis and differentiation as well as metastasis and chemoresistance. Indeed, worldwide literature has reported their involvement in the epithelial-mesenchymal transition (EMT) of different histotypes of cancer, being able to exploit peculiar features, for example, the possibility to act both in the nucleus and the cytoplasm. Moreover, SNHGs regulation is a fundamental topic to better understand their role in tumor progression albeit such mechanism is still debated. Here, we reviewed the biological functions of SNHGs in particular in the EMT process and discussed the perspectives for new cancer therapies.

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“…EMT is a complex biological process during which epithelial cells acquire the metastatic and invasive phenotypes of mesenchymal cells ( 31 , 32 ). EMT is highly associated with drug resistance, which results in the failure of standard chemotherapy ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Rac1 reverses enzalutamide resistance in castration‑resistant prostate cancer

et al. 2020

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Enzalutamide, an androgen receptor inhibitor, has been clinically approved for the treatment of metastatic castration-resistant prostate cancer (CRPC) in the United States. However, patients only benefit from enzalutamide for a short period of time as resistance may develop. Therefore, it is vital to develop a novel strategy to overcome enzalutamide resistance. Ras-related C3 botulinum toxin substrate 1 (Rac1), which is commonly upregulated in human cancer types, has been recognized as a key molecular component in tumorigenesis, invasion and metastasis. However, the role of Rac1 in enzalutamide-resistance in prostate cancer (PCa) remains unknown. In the present study, Rac1 was demonstrated to be upregulated in enzalutamide-resistant PCa cells, and Rac1 knockdown inhibited enzalutamide-resistant cell proliferation and colony formation. Western blotting results indicated that enzalutamide treatment downregulated the expression levels of JNK and activated transcription factor 2, as well as enhanced the Bax/Bcl-2 ratio and induced cleavage of poly-ADP ribose polymerase. Moreover, knockdown of Rac1 in MR49F cells significantly inhibited cell migration and invasion via the downregulation of Snail and the upregulation of E-cadherin. The results of a nude mouse xenograft tumor model using 22RV1 cells demonstrated that enzalutamide inhibited tumor growth after Rac1 knockdown dramatically, compared to vehicle and single treatment groups. Therefore, the present study provided novel evidence that Rac1 may serve a crucial role in enzalutamide resistance, and that targeting Rac1 may be a potential approach for the treatment of CRPC.

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EMT signaling: potential contribution of CRISPR/Cas gene editing

Cited by 23 publications

References 235 publications

Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer

Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer

Small nucleolar RNA host genes promoting epithelial–mesenchymal transition lead cancer progression and metastasis

Inhibition of Rac1 reverses enzalutamide resistance in castration‑resistant prostate cancer

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