Exploiting microRNAs As Cancer Therapeutics

Robb, Tamsin J.; Reid, Glen; Blenkiron, Cherie

doi:10.1007/s11523-017-0476-7

Cited by 21 publications

(14 citation statements)

References 168 publications

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Section: Discussionmentioning

confidence: 99%

“…There is strong evidence that miRNAs are tightly implicated in a mass of complex regulatory networks of crucial genes in a variety of tumors ( 52 - 54 ). It has been indicated that target genes of miRNAs are direct regulators of the hallmarks of cancer, including proliferation, cell cycle and cell apoptosis ( 52 ). Tao et al found that a decreased miR-125a expression in osteosarcoma tissues, and its overexpression contributed to growth suppression in osteosarcoma cells by downregulating E2F2 expression ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA-125a-5p enhances the sensitivity of esophageal squamous cell carcinoma cells to cisplatin by suppressing the activation of the STAT3 signaling pathway

Zhao

Yang

et al. 2018

Int J Oncol

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Increasing evidence has demonstrated that microRNAs (miRNAs or miRs) play a variety of roles in tumor development, progression and chemosensitivity in a wide range of tumors. In this study, we found that miR-125a-5p exhibited a low expression in esophageal squamous cell carcinoma (ESCC) tissues and cells, and that its low expression was associated with higher tumor staging and shorter a survival time of patients with ESCC. Moreover, miR-125a-5p overexpression contributed to the suppression of cell proliferation, cell cycle arrest, cell apoptosis and a decrease in cell migratory and invasive abilities, whereas the downregulation of miR-125a-5p promoted cell proliferation, accelerated cell cycle progression, suppressed apoptosis and enhanced the migratory and invasive abilities of ESCC EC1 and TE1 cells, which may be tightly associated with the epithelial-mesenchymal transition (EMT) process in ESCC. Importantly, miR-125a-5p enhanced the cytotoxic effects of cisplatin on EC1 and TE1 cells, and co-treatment with miR-125a-5p and cisplatin significantly induced cell apoptosis and reduced the cell migratory and invasive abilities of EC1 and TE1 cells, coupled with an increase in the E-cadherin level and a decrease in the N-cadherin and Vimentin levels. Most notably, signal transducer and activator of transcription-3 (STAT3) was found to be a direct target of miR-125a-5p in ESCC cells, and miR-125a-5p overexpression significantly reduced the protein levels of t-STAT3, p-STAT3 and vascular endothelial growth factor (VEGF) in EC1 and TE1 cells. Furthermore, the combination of miR-125a-5p and cisplatin markedly inactivated the STAT3 signaling pathway; however, interleukin (IL)-6, a widely reported activator of the STAT3 signaling pathway, reversed the suppressive effects of miR-125a-5p/cisplatin in ESCC cells on the activation of the STAT3 signaling pathway. Of note, we found that IL-6 markedly reversed the altered cell phenotype mediated by the combination of miR-125a-5p and cisplatin in ESCC cells. These findings suggest that miR-125a-5p may play a pivotal role in the development and progression of ESCC, which may be achieved via the manipulation of the STAT3 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MicroRNA-125a-5p enhances the sensitivity of esophageal squamous cell carcinoma cells to cisplatin by suppressing the activation of the STAT3 signaling pathway

Zhao

Yang

et al. 2018

Int J Oncol

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“…These results suggest that miRNA-based therapies may become a viable strategy for treating a broad range of disorders such as cancer and cardiovascular disease, among others (van Rooij and Kauppinen, 2014 ; Adams et al, 2017 ). Further, in oncology the aim is to downregulate or block the function of oncogenic miRNAs and/or upregulate expression of tumor suppressor miRNAs, for which different miRNA-targeting strategies have been proposed (as reviewed in Ling et al, 2013 ; Li and Rana, 2014 ; Robb et al, 2017 ). Replacement of tumor suppressor miRNAs typically involves the introduction of synthetic miRNA mimics or miRNA expression vectors.…”

Section: Overview Of Mirna Biogenesis and Functionmentioning

confidence: 99%

The Emerging Role of microRNAs in Aquaporin Regulation

et al. 2018

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Aquaporins (AQPs) are membrane channels widely distributed in human tissues. AQPs are essential for water and energy homeostasis being involved in a broad range of pathophysiological processes such as edema, brain injury, glaucoma, nephrogenic diabetes insipidus, salivary and lacrimal gland dysfunction, cancer, obesity and related metabolic complications. Compelling evidence indicates that AQPs are targets for therapeutic intervention with potential broad application. Nevertheless, efficient AQP modulators have been difficult to find due to either lack of selectivity and stability, or associated toxicity that hamper in vivo studies. MicroRNAs (miRNAs) are naturally occurring small non-coding RNAs that regulate post-transcriptional gene expression and are involved in several diseases. Recent identification of miRNAs as endogenous modulators of AQP expression provides an alternative approach to target these proteins and opens new perspectives for therapeutic applications. This mini-review compiles the current knowledge of miRNA interaction with AQPs highlighting miRNA potential for regulation of AQP-based disorders.

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“…How this might be achieved requires a more nuanced understanding of the regulation of miR-155 expression in different cellular contexts. MicroRNA-based therapy offers significant promise that has seen multiple ongoing preclinical and early-phase human trials, although it should be pointed out that substantial hurdles remain regarding the safety of high/frequent dose regimes and targeted delivery strategies [71].…”

Section: Clinical Implications Of Mir-155 Expression In Amlmentioning

confidence: 99%

MicroRNA-155 expression and function in AML: An evolving paradigm

Narayan

Bracken

Ekert

2018

Experimental Hematology

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Acute myeloid leukemia (AML) arises when immature myeloid blast cells acquire multiple, recurrent genetic and epigenetic changes that result in dysregulated proliferation. Acute leukemia is the most common form of pediatric cancer, with AML accounting for ~20% of all leukemias in children. The genomic aberrations that drive AML inhibit myeloid differentiation and activate signal transduction pathways that drive proliferation. MicroRNAs, a class of small (~22 nucleotide) noncoding RNAs that posttranscriptionally suppress the expression of specifically targeted transcripts, are also frequently dysregulated in AML, which may prove useful for the purposes of disease classification, prognosis, and future therapeutic approaches. MicroRNA expression profiles are associated with patient prognosis and responses to standard chemotherapy, including predicting therapy resistance in AML. miR-155 is the primary focus of this review because it has been repeatedly associated with poorer survival across multiple cohorts of adult and pediatric AML. We discuss some novel features of miR-155 expression in AML, in particular how the levels of expression can critically influence function. Understanding the role of microRNAs in AML and the ways in which microRNA expression influences AML biology is one means to develop novel and more targeted therapies.

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Exploiting microRNAs As Cancer Therapeutics

Cited by 21 publications

References 168 publications

MicroRNA-125a-5p enhances the sensitivity of esophageal squamous cell carcinoma cells to cisplatin by suppressing the activation of the STAT3 signaling pathway

MicroRNA-125a-5p enhances the sensitivity of esophageal squamous cell carcinoma cells to cisplatin by suppressing the activation of the STAT3 signaling pathway

The Emerging Role of microRNAs in Aquaporin Regulation

MicroRNA-155 expression and function in AML: An evolving paradigm

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