Autophagy-Regulating microRNAs and Cancer

Gözüaçık, Devrim; Akkoç, Yunus; Öztürk, Deniz Gülfem; Koçak, Muhammed

doi:10.3389/fonc.2017.00065

Cited by 147 publications

(116 citation statements)

References 257 publications

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“…miRNAs are a general class of endogenous noncoding RNAs of 22–25 nucleotides, widely existing in diverse species, and playing essential roles in cell proliferation, immune response, and maintaining homeostasis . miRNAs can control the expression of nearly 30% of protein‐coding genes by targeting a sequence located in the 3′‐untranslated region (3′‐UTR) of the target genes, resulting in cleavage or inhibition of translation and causing profound changes in protein levels . Moreover, a single miRNA can simultaneously regulate multiple target genes within a genetic network, resulting in potent cumulative effects on gene networks and affect many biological processes and diseases.…”

Section: Introductionmentioning

confidence: 99%

“…50-52 miRNAs can control the expression of nearly 30% of protein-coding genes by targeting a sequence located in the 3 0 -untranslated region (3 0 -UTR) of the target genes, resulting in cleavage or inhibition of translation and causing profound changes in protein levels. [53][54][55] Moreover, a single miRNA can simultaneously regulate multiple target genes within a genetic network, resulting in potent cumulative effects on gene networks and affect many biological processes and diseases. The miRNAs formation involved three steps; the first step is when the miRNAs DNA loci transcribed by RNA polymerase II into long primary miRNA transcripts (pri-miRNAs).…”

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confidence: 99%

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MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

et al. 2019

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Autophagy is a highly conserved catabolic process and fundamental biological process in eukaryotic cells. It recycles intracellular components to provide nutrients during starvation and maintains quality control of organelles and proteins. In addition, autophagy is a well‐organized homeostatic cellular process that is responsible for the removal of damaged organelles and intracellular pathogens. Moreover, it also modulates the innate and adaptive immune systems. Micro ribonucleic acids (microRNAs) are a mature class of post‐transcriptional modulators that are widely expressed in tissues and organs. And, it can suppress gene expression by targeting messenger RNAs for translational repression or, at a lesser extent, degradation. Research indicates that microRNAs regulate autophagy through different pathways, playing an essential role in the treatment of various diseases. It is an important regulator of fundamental cellular processes such as proliferation, autophagy, and cell apoptosis. In this review article, we first review the current knowledge of autophagy and the function of microRNAs. Then, we summarize the mechanism of autophagy and the signaling pathways related to autophagy by citing at least the main proteins involved in the different phases of the process. Second, we introduce other members of RNA and report some examples in various pathologies. Finally, we review the current literature regarding microRNA‐based therapies for cancer, atherosclerosis, cardiac disease, tuberculosis, and viral diseases. MicroRNAs can cause autophagy upregulation or downregulation by targeting genes or affecting autophagy‐related signaling pathways. Therefore, the microRNAs have a huge potential in autophagy regulation, and it is the function as diagnostic and prognostic markers.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

et al. 2019

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“…In addition, miRNAs are involved in tumorigenesis and progression of malignancies via different mechanisms, including control of cell cycle [21, 22], apoptosis [23, 24], autophagy [25], epithelial-mesenchymal transition [26], drug resistance [27] and metabolic reprogramming [28]. All of the above data indicate that miRNAs have the potential to be novel diagnostic and prognostic biomarkers for malignant tumors.…”

Section: Discussionmentioning

confidence: 99%

Potential Targets and Clinical Value of MiR-224-5p in Cancers of the Digestive Tract

Zhang

Huang

Chen

2017

Cell Physiol Biochem

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Background/Aims: MicroRNAs participate in various biological processes in malignant tumors. However, the mechanisms of miR-224-5p in digestive system cancers are not fully understood. A comprehensive investigation of the clinical value and potential targets of miR-224-5p in cancers of the digestive tract is necessary. Methods: Expression profiling data and related-prognostic data of miR-224-5p were acquired from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress, and published literature. The potential target mRNAs of miR-224-5p were predicted using bioinformatics methods and finally annotated using Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: MiR-224-5p is up-regulated in digestive system cancers (SMD=0.69, 95% CI: 0.43-0.96, P<0.0001) and exhibits a moderate diagnostic ability (AUC=0.84, 95% CI: 0.80-0.87). Our data also demonstrated that miR-224-5p is statistically significantly correlated with overall survival univariate analysis (HR=1.69, 95% CI: 1.15-2.49, P=0.007) and multivariate analysis (HR=2.39, 95% CI: 1.74-3.30, P<0.0001). In total, 388 potential miR-224-5p target mRNAs were predicted by bioinformatics methods. GO annotation analysis revealed that the top terms of miR-224-5p in biological process, cellular component and molecular function were system development, neuron part, and transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding, respectively. Moreover, eight pathways were identified in KEGG pathway enrichment analysis. Conclusions: MiR-224-5p is up-regulated and has the potential to become a diagnostic and prognostic biomarker in digestive system cancers. MiR-224-5p might play vital roles in cancers of the digestive tract but the exact molecular mechanisms need further study and verification.

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“…Interestingly, many autophagy genes (e.g., BECLIN‐1 ) act as oncosuppressors. The expression of autophagy genes and of autophagy‐regulating genes is modulated also at epigenetic level through histone deacetylation and promoter methylation events, as well as by certain micro‐RNAs . This fact opens the possibility that environmental factors could affect the level of autophagy in a cell lineage in a chronic “stable” manner.…”

Section: Autophagy In Cancer and Its Modulation By Microenvironmentalmentioning

confidence: 99%

The metabolic cross‐talk between epithelial cancer cells and stromal fibroblasts in ovarian cancer progression: Autophagy plays a role

Thuwajit

Ferraresi

Titone

et al. 2017

Medicinal Research Reviews

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Cancer and stromal cells, which include (cancer‐associated) fibroblasts, adipocytes, and immune cells, constitute a mixed cellular ecosystem that dynamically influences the behavior of each component, creating conditions that ultimately favor the emergence of malignant clones. Ovarian cancer cells release cytokines that recruit and activate stromal fibroblasts and immune cells, so perpetuating a state of inflammation in the stroma that hampers the immune response and facilitates cancer survival and propagation. Further, the stroma vasculature impacts the metabolism of the cells by providing or limiting the availability of oxygen and nutrients. Autophagy, a lysosomal catabolic process with homeostatic and prosurvival functions, influences the behavior of cancer cells, affecting a variety of processes such as the survival in metabolic harsh conditions, the invasive growth, the development of immune and chemo resistance, the maintenance of stem‐like properties, and dormancy. Further, autophagy is involved in the secretion and the signaling of promigratory cytokines. Cancer‐associated fibroblasts can influence the actual level of autophagy in ovarian cancer cells through the secretion of pro‐inflammatory cytokines and the release of autophagy‐derived metabolites and substrates. Interrupting the metabolic cross‐talk between cancer cells and cancer‐associated fibroblasts could be an effective therapeutic strategy to arrest the progression and prevent the relapse of ovarian cancer.

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Autophagy-Regulating microRNAs and Cancer

Cited by 147 publications

References 257 publications

MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

Potential Targets and Clinical Value of MiR-224-5p in Cancers of the Digestive Tract

The metabolic cross‐talk between epithelial cancer cells and stromal fibroblasts in ovarian cancer progression: Autophagy plays a role

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