miR-875-5p counteracts epithelial-to-mesenchymal transition and enhances radiation response in prostate cancer through repression of the EGFR-ZEB1 axis

Bezawy, Rihan El; Cominetti, Denis; Fenderico, Nicola; Zuco, Valentina; Beretta, Giovanni Luca; Dugo, Matteo; Arrighetti, Noemi; Stucchi, C.; Rancati, T.; Valdagni, Riccardo; Zaffaroni, Nadia; Gandellini, Paolo

doi:10.1016/j.canlet.2017.02.033

Cited by 83 publications

(60 citation statements)

References 32 publications

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“…2). Accordingly, EMT might be neutralized using miR-875-5p, which mediates EGFR downregulation in PCa cells, promoting a radiosensitizing effect (El Bezawy et al, 2017). Additionally, the inhibition of VEGFR (VEGF receptor) expression using three artificial miRNA in PCa cells and xenograft mouse models showed a synergistic effect with standard chemotherapy and was associated with EMT inhibition (Huang et al, 2017).…”

Section: Are Anti-emt Therapies Feasible?mentioning

confidence: 99%

EMT: Present and future in clinical oncology

et al. 2017

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Epithelial/mesenchymal transition (EMT) has emerged as a key regulator of metastasis by facilitating tumor cell invasion and dissemination to distant organs. Recent evidences support that the reverse mesenchymal/epithelial transition (MET) is required for metastatic outgrowth; moreover, the existence of hybrid epithelial/mesenchymal (E/M) phenotypes is increasingly being reported in different tumor contexts. The accumulated data strongly support that plasticity between epithelial and mesenchymal states underlies the dissemination and metastatic potential of carcinoma cells. However, the translation into the clinics of EMT and epithelial plasticity processes presents enormous challenges and still remains a controversial issue. In this review, we will evaluate current evidences for translational applicability of EMT and depict an overview of the most recent EMT in vivo models, EMT marker analyses in human samples as well as potential EMT therapeutic approaches and ongoing clinical trials. We foresee that standardized analyses of EMT markers in solid and liquid tumor biopsies in addition to innovative tools targeting the E/M states will become promising strategies for future translation to the clinical setting.

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Section: Are Anti-emt Therapies Feasible?mentioning

confidence: 99%

EMT: Present and future in clinical oncology

et al. 2017

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“…Zinc finger E-Box binding homeobox 1 (ZEB1) has been proven to be critical for the regulation of checkpoint kinase 1, which coordinates DNA damage response signaling [66]. Also, PKCε could activate the DNA-dependent protein kinase by modulating the nuclear accumulation of the epidermal growth factor receptor [67].…”

Section: Mir-205-5p and Mir-211-5pmentioning

confidence: 99%

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Seo

Moeng

Sim³

et al. 2019

Cells

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The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.Cells 2020, 9, 29 2 of 32 to confer the ability to acquire CSC properties onto cancer cells, thereby contributing to therapeutic resistance [7]. Moreover, cell-to-cell communication via extracellular vesicles among different types of cells within the cancer microenvironment could affect the efficacy of cancer therapies by delivering miRNAs that regulate various signaling pathways connected to therapeutic resistance [8,9].Combination therapies have been proposed to overcome therapeutic resistance via the combined inhibition of different mechanisms. For example, the combination of cobimetinib and pictilisib was reported to be beneficial for the treatment of colorectal cancer cells. However, resistance is unavoidable even after the combination treatment [10]. Similarly, the simultaneous inhibition of phosphoinositide 3-kinase (PI3K) and a mechanistic target of rapamycin kinase (mTOR) was reported to activate extracellular signal-regulated kinase (ERK), a pro-survival factor, in acute myeloid leukemia [11]. Therefore, it is still necessary to explore new combination strategies to defeat therapeutic resistance. An improved understanding of the cellular basis of cancer therapeutic resistance can further provide promising opportunities to design and develop novel cancer treatment strategies to manage cancers.MicroRNAs (miRNAs) are widely recognized, small, regulatory RNAs modulating numerous intracellular signaling pathways in several diseases, including cancers. Based on the expression levels and intracellular functions of miRNAs, they could act as tumor-suppressive or oncogenic factors in cancer cells [12][13][14]. The abnormal expression of miRNAs is associated with therapeutic resistance in cancer, and the modulation of m...

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“…[14][15][16] Accumulating evident showed that miR-875-5p plays a crucial role in the regulation of epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma and prostate cancer progression. 17,18 Because EMT is a process for an epithelial cell to undergo a conversion to a mesenchymal phenotype, EMT of HSCs may have a central role in liver fibrosis progression.…”

Section: Introductionmentioning

confidence: 99%

Icariin‐induced miR‐875‐5p attenuates epithelial‐mesenchymal transition by targeting hedgehog signaling in liver fibrosis

Zhao

2019

J of Gastro and Hepatol

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Background Hepatic fibrosis is the final endpoint for most chronic liver diseases and remains a significant public health problem worldwide. Icariin, a naturally occurring flavonol glucoside, has been reported to exhibit protective effects on liver injury and alleviate liver fibrosis. However, the underlying detail molecular mechanism is not fully revealed. Methods Mouse primary hepatic stellate cells (HSCs) and carbon tetrachloride (CCL4)‐induced liver fibrosis model in mice were used as in vitro and in vivo models in this study. The expression levels of miR‐875‐5p were detected by quantitative reverse transcription‐PCR. The validation of the direct target of miR‐875‐5p was through dual‐luciferase reporter assay and western blotting assay. The cell proliferation and cell mobility were determined using MTT assay and Transwell migration assay, respectively. Results We found that icariin inhibited epithelial–mesenchymal transition and collagen protein section of HSCs. Icariin exerted hepatoprotective effects on mice model of CCL4‐induced liver fibrosis. Our further results revealed that miR‐875‐5p was downregulated in human cirrhosis tissues and activated murine HSCs. Icariin induced miR‐875‐5p upregulation and subsequently decreased glioma‐associated oncogene homolog 1 (GLI1) expression through direct binding to the three prime untranslated region of GLI1 mRNA. Conclusion Our study highlighted the potential therapeutic application of icariin for liver fibrosis management.

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miR-875-5p counteracts epithelial-to-mesenchymal transition and enhances radiation response in prostate cancer through repression of the EGFR-ZEB1 axis

Cited by 83 publications

References 32 publications

EMT: Present and future in clinical oncology

EMT: Present and future in clinical oncology

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Icariin‐induced miR‐875‐5p attenuates epithelial‐mesenchymal transition by targeting hedgehog signaling in liver fibrosis

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