Epitranscriptomics: A New Layer of microRNA Regulation in Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. miRNAs: Biogenesis and Functions
3. Epitranscriptomic Modifications of miRNA in Cancer
3.1. N6-Methyl-Adenosine (m6A)
Cancer Type | m6A-Modified miRNA(s) | Increase/ Decrease 1 | Effects on miRNA Processing/Function | Effects on Tumor Progression | Reference |
---|---|---|---|---|---|
Colorectal Cancer | miR-1246 | ↑ | processing | Up-regulation of mature of miR-1246 results in the reduction of SPRED2, thus activating the RAF/MEK/ERK pathway | [85] |
miR-375 | ↓ | processing | Down-regulation of mature miR-375 increases the expression of its targets YAP1 and SP1 thus increasing proliferation, and migration and invasion | [83] | |
miR-483, miR-676 miR-877 | n.d. | processing | miR-483, miR-676 and miR-877 modulate mitochondrial metabolism by targeting electron transport chain genes | [90] | |
miR-17-5p let-7a-5p | ↑ | Binding to targets | n.d. | [91] | |
Pancreatic cancer | miR-25-3p | ↑ | processing | Up-regulation of mature miR-25-3p results in the reduction of PHLPP2, leading to AKT activation. | [89] |
miR-17-5p let-7a-5p | ↑ | Binding to targets | n.d. | [91] | |
Hepatocellular Carcinoma | miR-126 | ↓ | processing | Down-regulation of mature miR-126 which acts as a tumor suppressor | [82] |
Bladder cancer | miR-221/222 | ↑ | processing | Up-regulation of mature miR-221/222 results in the reduction of PTEN, leading to proliferation | [84] |
Gallbladder cancer | miRNA-92 | ↑ | processing | Up-regulation of mature miRNA-92 results in the reduction of PTEN, thus activating PI3K/AKT signaling | [88] |
Ovarian cancer | miR-126 | ↑ | processing | Up-regulation of mature miR-126-5p results in the reduction of PTEN, thus activating the PI3K/Akt/mTOR pathway | [87] |
Gastric cancer | miR-17-5p let-7a-5p | ↑ | Binding to targets | n.d. | [91] |
Lung cancer (brain metastasis) | miR-143-3p | ↑ | processing | Up-regulation of mature miR-143-3p promotes the metastatic potential of lung cancer via regulation of angiogenesis and microtubules through VASH1 | [86] |
3.2. A-to-I Editing
Cancer | A-to-I-Modified miRNA(s) | Increase/ Decrease 1 | Effects on miRNA Processing/Function | Effects on Tumor Progression | Reference |
---|---|---|---|---|---|
Glioma | mir-376a-5p | ↓ | Binding to targets | Unedited miR-376a-5p promotes aggressive glioma growth, by its ability to target RAP2A and concomitant inability to target AMFR | [125] |
miR-221/222 miR-21 | ↓ | processing | Up-regulation of mature miR-221/222 and miR-21 results in the repression of its targets p27Kip1 and PDCD4, thus increasing proliferation and migration of glioblastoma | [118] | |
miR-589-3p | ↓ | Binding to targets | Editing within miR-589–3p retargets the miRNA from the protocadherin PCDH9 to the metalloprotease ADAM12, which is involved in glioblastoma cell invasion. | [129] | |
Melanoma | miR-455-5p | ↓ | Binding to targets | Unedited miR-455-5p but not the edited form targets the tumor suppressor gene CPEB1, thus promoting tumor growth and metastasis | [127] |
miR-378a-3p | ↓ | Binding to targets | Edited miR-378a-3p but not the unedited form specifically targets the PARVA oncogene, thus preventing the progression of melanoma towards the malignant phenotype | [128] | |
Chordoma | miR-10a miR-125a | ↑ | processing | Down-regulation of miR-10a and miR-125a expression and upregulates expression of their target genes | [119] |
Chronic myeloid leukemia | let-7 | ↑ | processing | Down-regulation of mature let-7 results in increased LIN28B expression and enhanced self-renewal | [120] |
Thyroid cancer | miR-200b | ↑ | Binding to targets | Edited miR-200b has weakened activity against its target gene ZEB1, an epithelial–mesenchymal transition (EMT) marker | [131] |
Lung cancer | miR-381 | ↑ | n.d. | Edited miR-381 enhances the growth of non-small-cell lung cancer cells as compared to the unedited form | [134] |
3.3. 5-Methylcytosine (m5C)
3.4. N7-Methylguanosine (m7G)
4. Epitranscriptomic Modifications of miRNA Targets
4.1. m6A in miRNA Targets
4.2. A-to-I Editing in miRNA Targets
4.3. m5C in miRNA Targets
5. Methodological Challenges and the Potential Limits of Current Knowledge
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Cancer | Modified miRNA(s) | Increase/ Decrease 1 | Effects on miRNA Processing/Function | Effects on Tumor Progression | Reference |
---|---|---|---|---|---|
Glioma | miRNA-181a-5p (m5C) | ↑ | Binding to targets | Cytosine-methylated miRNA-181a-5p loses its ability to target the mRNA of the pro-apoptotic protein BIM | [169] |
Colorectal cancer; gastric cancer; pancreatic cancer | miR-200c-3p miR-21-3p (m5C) | ↑ | Binding to targets | n.d. | [88] |
Lung cancer | let-7 family (m7G) | n.d. | processing | m7G methylation within miRNAs regulates cell migration | [173] |
Colon cancer | let-7e (m7G) | ↓ | processing | Down-regulation of mature let-7e results in the activation of its targets HMGA2 thus stimulating colon cancer cell viability and mobility | [174] |
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De Paolis, V.; Lorefice, E.; Orecchini, E.; Carissimi, C.; Laudadio, I.; Fulci, V. Epitranscriptomics: A New Layer of microRNA Regulation in Cancer. Cancers 2021, 13, 3372. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13133372
De Paolis V, Lorefice E, Orecchini E, Carissimi C, Laudadio I, Fulci V. Epitranscriptomics: A New Layer of microRNA Regulation in Cancer. Cancers. 2021; 13(13):3372. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13133372
Chicago/Turabian StyleDe Paolis, Veronica, Elisa Lorefice, Elisa Orecchini, Claudia Carissimi, Ilaria Laudadio, and Valerio Fulci. 2021. "Epitranscriptomics: A New Layer of microRNA Regulation in Cancer" Cancers 13, no. 13: 3372. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13133372