MicroRNAs and other non-coding RNAs as targets for anticancer drug development

Ling, Hui; Fabbri, Muller; Calin, George A.

doi:10.1038/nrd4140

Cited by 1,298 publications

(1,035 citation statements)

References 179 publications

(224 reference statements)

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“…The pre-miRNA is then exported to the cytoplasm and cleaved by Dicer into double stranded miRNAs. [24][25][26] It has been reported that Drosha associates with dozens of distinct polypeptides, including DGCR8, to form a large 'microprocessor' Drosha complex. 27 The processing of primiRNA by the Drosha complex takes place concurrently with or shortly after transcription.…”

Section: Discussionmentioning

confidence: 99%

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy

et al. 2016

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Radioresistance is a major obstacle in successful clinical cancer radiotherapy, and the underlying mechanisms are not clear. Here we show that IKKα-mediated miR-196a biogenesis via interaction with Drosha regulates the sensitivity of nasopharyngeal carcinoma (NPC) cells to radiotherapy. Phosphorylation of IKKα at T23 site (p-IKKαT23) promotes the binding of IKKα to Drosha that accelerates the processing of miR-196a primary transcripts, leading to increased expressions of both precursor and mature miR-196a. Dephosphorylation of p-IKKαT23 downregulates miR-196a expression and promotes the resistance of NPC cells to radiation treatment. The miR-196a mimic suppresses while its inhibitor promotes the resistance of NPC to radiation treatment. Importantly, the expression of p-IKKαT23 is positively related to the expression of miR-196a in human NPC tissues, and expression of p-IKKαT23 and miR-196a is inversely correlated with NPC clinical radioresistance. Thus, our studies establish a novel mechanistic link between the inactivation of IKKαT23-Drosha-miR-196a pathway and NPC radioresistance, and de-inactivation of IKKαT23-Drosha-miR-196a pathway would be an efficient way to restore the sensitivity of radioresistant NPC to radiotherapy.

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Section: Discussionmentioning

confidence: 99%

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy

et al. 2016

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“…As cancer‐specific miRNAs are master regulators of many critical oncogenic pathways, their utilization for cancer diagnosis and as promising potential therapeutic target for clinical treatment strategies or personalized medicine is becoming more and more clear (Ling et al ., 2013). After discovering the role of miRNAs in cell–cell signaling and TME, targeting miRNAs as anticancer therapeutic strategy is becoming more realistic and promising.…”

Section: Novel Mirna‐based Therapeutic Approachesmentioning

confidence: 99%

Cell‐to‐cell communication: microRNAs as hormones

2017

Self Cite

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Mammalian cells can release different types of extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies. Accumulating evidence suggests that EVs play a role in cell‐to‐cell communication within the tumor microenvironment. EVs’ components, such as proteins, noncoding RNAs [microRNAs (miRNAs), and long noncoding RNAs (lncRNAs)], messenger RNAs (mRNAs), DNA, and lipids, can mediate paracrine signaling in the tumor microenvironment. Recently, miRNAs encapsulated in secreted EVs have been identified in the extracellular space. Mature miRNAs that participate in intercellular communication are released from most cells, often within EVs, and disseminate through the extracellular fluid to reach remote target cells, including tumor cells, whose phenotypes they can influence by regulating mRNA and protein expression either as tumor suppressors or as oncogenes, depending on their targets. In this review, we discuss the roles of miRNAs in intercellular communication, the biological function of extracellular miRNAs, and their potential applications for diagnosis and therapeutics. We will give examples of miRNAs that behave as hormones.

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“…Therefore, an ideal targeted therapy should focus on many key coding and/or regulatory sequences involved in the process of carcinogenesis. A significant advantage of using miRNAs as potential targets and/or treatment agents is their ability to regulate the expression of a number of genes and non-coding sequences that are associated with a single pathway or are involved in the regulation of parallel signalling pathways that control tumour development [165]. Compared with treatment based on small interfering RNAs (siRNAs), each of which can only silence one gene, the use of miRNAs as treatment agents seems much more beneficial.…”

Section: Mirnas As Therapeutic Agents In Nsclc Treatmentmentioning

confidence: 99%

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

Florczuk¹,

Szpechcinski²,

Chorostowska‐Wynimko³

2017

Targ Oncol

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Lung cancer is the most common cancer worldwide. Up to 85% of lung cancer cases are diagnosed as nonsmall cell lung cancer (NSCLC). The effectiveness of NSCLC treatment is expected to be improved through the implementation of robust and specific biomarkers. MicroRNAs (miRNAs) are small, non-coding molecules that play a key role in the regulation of basic cellular processes, including differentiation, proliferation and apoptosis, by controlling gene expression at the post-transcriptional level.

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MicroRNAs and other non-coding RNAs as targets for anticancer drug development

Cited by 1,298 publications

References 179 publications

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy

Cell‐to‐cell communication: microRNAs as hormones

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

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