Splice and Dice: Intronic microRNAs, Splicing and Cancer
Abstract
:1. Introduction
2. Biogenesis of Intronic miRNAs
2.1. Co-Transcriptional Processing of Intronic miRNAs
2.2. Mirtrons and the Non-Canonical miRNA Pathway
2.3. Comparisons and Contrasts between Mirtrons and Canonical Intronic miRNAs
3. Interplay between miRNA Processing and the Spliceosome
3.1. Kinetic Regulation of Microprocessing and Splicing
3.2. Splicing Factors Regulating Microprocessing
3.3. Role of RNA m6A Modification
3.4. The Microprocessor as a Splicing Factor
3.5. Alternative Splicing and miRNA Biogenesis
4. Intronic miRNAs—Host Gene Interactions and Their Roles in Cancer
4.1. mir-615-3p/HOXC5 Axis and Telomerase Regulation
4.2. miR-374b/miR-545/FTX
4.3. miR-944/TP63 Axis and p53 Maintenance
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Mirtron | Type | Host Gene and Intron | Validated Gene Targets | Cancer |
---|---|---|---|---|
hsa-miR-877 | Mirtron | ABCF1 Intron 12 | ACP5 [52], AQP3 [53], ATXN7L3 [54], CCNA2 [55], CD274 [56], CDK14 [57], CDKN2A (upreg) [58], FGF2 [59], FOXM1 [60], FOXP4 [61], IGF1R [62], MACC1 [63], MTDH [64], PIK3R3 [65], PMEPA1 [66], STARD13 [67], SUZ12 [68], TLR4 [69], VEGFA [70] | Bladder (TS) [58], Cervical (TS) [54,59,63], Colorectal (TS) [64], Gastric (TS) [53,56,70], Glioma (Onc) [69], Glioma (TS) [68], Laryngeal (TS) [61], Liver (TS) [57,60,65], Lung (TS) [52,55,62], Oesophageal (TS) [66], Pancreatic (Onc) [67] |
hsa-miR-1224 | Mirtron | VWA5B2 Intron 17 | CREB1 [71], ELF3 [72], ETV1 [73], FAK [74], KLF3 [75], PGM5 [76], PLK1 [77], RSF1 [78], SLC29A3 [79], SP1 [80], SND1 [81,82], TGFBR2 [83], TNS4 [84], | Breast (Onc) [76], Colorectal (TS) [80], Gastric (TS) [74,78], Glioma (TS) [71,83], Lung (TS) [73,75], Oesophageal (TS) [84], Osteosarcoma (TS) [77], Ovarian (TS) [81], Pancreatic (TS) [72], Prostate (TS) [82], Rectal (TS) [79] |
hsa-miR-1226 | Mirtron | DHX30 Intron 20 | AKT1 [85], AQP5 [86], DUSP4 [87], ERBB2 [85], ITGB1 [88], MUC1 [89], PIK3R2 [85] | Breast (TS) [85,86,89], Liver (TS) [87,88], |
hsa-miR-1227 | Mirtron | PLEKHJ1 Intron 1 | IRF2 [90], MAPK13 [91], SUPT16H [92] | Endometrial (TS) [91], Lung (TS) [92], Osteosarcoma (Onc) [90], |
hsa-miR-1228 | Mirtron | LRP1 Intron 48 | CSNK2A2 [93], MIF [94], MMP14 [95], SCAI [96,97], SOX17 [98], TCF21 [99], TP53 [100,101], | Breast (Onc) [96,98], Gastric (TS) [93,94,95], Liver (Onc) [101], Lung (Onc) [99], Osteosarcoma (Onc) [97], Ovarian (Onc) [100] |
hsa-miR-1229 | Mirtron | MGAT4B Intron 1 | APC [102], GSK3B [102], HIPK2 [103], ICAT [102], ITGB8 [104], MTOR [105], | Breast (Onc) [102], Colorectal (Onc) [103], Glioma (TS) [104,105], |
hsa-miR-1236 | Mirtron | RDBP Intron 7 | AFP [106], ATG7 [107], CHD4 [108], CDKN1A (upreg) [109], HDAC3 [110], HMGB1 [111], HOXB7 [112,113], KLF8 [114], MTA2 [115], SENP1 [110], SLC9A1 [116], TPT1 [117], TRIM37 [118], ZEB1 [119,120], | Breast (TS) [108,116,120], Cervical (TS) [118], Colorectal (TS) [112], Gastric (TS) [111,115], Glioma (TS) [113], Lung (TS) [107,114,117], Liver (TS) [106], Kidney (TS) [109], Ovarian (TS) [119], |
hsa-miR-937 | 3′-tailed mirtron | SCRIB Intron 29 | APAF1 [121], CCRL2 [122], FOXQ1 [123], INPP4B [124], SOX17 [125], TIMP3 [126], | Breast (Onc) [121,125], Breast (TS) [123], Colorectal (Onc) [126], Lung (Onc) [124], |
hsa-miR-939 | 5′-tailed mirtron | CPSF1 Intron 4 | APC2 [127], ARHGAP4 [128], BCL2L1 [129,130], CDH5 [131], HDGF [132], IGF1R [133], JUNB [134], LIMK2 [135], NGFR [136], SLC34A2 [137], TIMP2 [138], | Breast (Onc) [131], Colorectal (TS) [130,135], Gastric (TS) [137], Lung (Onc) [138], Lymphoma (TS) [134], Ovarian (Onc) [127], Osteosarcoma (TS) [133], Pancreatic (Onc) [128], Prostate (TS) [132], |
hsa-miR-1292 | 5′-tailed mirtron | NOP56 Intron 11 | DEK [139] | Gastric (TS) [139], |
hsa-miR-1976 | 5′-tailed mirtron | RPS6KA1 Intron 6 | PIK3CG [140], PLCE1 [141], | Breast (TS) [140], Lung (TS) [141], |
hsa-miR-4728 | 5′-tailed mirtron | ERBB2 Intron 25 | CAV1 [142], COL1A2 [142], EBP1 [143], ESR1 [144], MST4 [145], PAPD5 [146], THBS2 [142] | Breast (Onc) [143,146], Breast (TS) [145], Colorectal (TS) [142], Lung (TS) [147], |
hsa-miR-6838 | 5′-tailed mirtron | POLM Intron 10 | GPRIN3 [148], WNT3A [149], | Breast (TS) [149], Gastric (TS) [148] |
hsa-miR-6852 | 5′-tailed mirtron | TLN1 Intron 24 | FOXJ1 [150], LEF1 [151], ICAM1 [152], TCF7 [153], | Colorectal (TS) [153], Gastric (TS) [150], Glioma (TS) [151], Liver (TS) [152] |
miRNA | Host Gene | Cancer | Functional Association |
---|---|---|---|
hsa-miR-196b | HOXA9 | Mixed lineage leukemia | Complex: miR-196b directly targets its host gene HOXA9 (oncogene) but also targets FAS (tumor suppressor) [205] |
hsa-miR-204 | TRPM3 | Renal (Clear cell) | Antagonism: inhibits TRPM3-induced proliferation by directly targeting TRPM3; also inhibits oncogenic autophagy by targeting LC3B [206] |
hsa-miR-326 | ARBB1 | Medulloblastoma | Synergism: inhibits E2F1-associated pro-survival function by directly targeting E2F1 (miR-326) and E2F1 acetylation (ARBB1) [207] |
hsa-miR-342 | EVL | Lymphoid leukemia | Antagonism: miR-342/EVL balance determines myeloid (high miR-342) or lymphoid (high EVL) differentiation. miR-342 antagonises EVL-induced lymphoid proliferation [208] |
hsa-miR-675 | H19 | Breast | Synergism: both promote cell migration, invasiveness and stemness [209] |
hsa-miR-1204/ 1205/ 1207 | PVT1 | Various | Synergism: PVT1 sponges multiple miRNAs, thereby enhancing tumor proliferation induced by miR-1204, miR-1205 and miR-1207 [210] |
hsa-miR-3189 | GDF15 | Various | Antagonism: mir-3189 promotes p53-independent apoptosis; GDF15 is implicated in metastasis [211] |
hsa-miR-4728 | ERBB2 | Breast | Synergism: inhibits apoptosis thereby promoting therapy resistance to HER2(ERBB2) inhibitors [212] |
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Wong, A.C.H.; Rasko, J.E.J. Splice and Dice: Intronic microRNAs, Splicing and Cancer. Biomedicines 2021, 9, 1268. https://doi.org/10.3390/biomedicines9091268
Wong ACH, Rasko JEJ. Splice and Dice: Intronic microRNAs, Splicing and Cancer. Biomedicines. 2021; 9(9):1268. https://doi.org/10.3390/biomedicines9091268
Chicago/Turabian StyleWong, Alex C. H., and John E. J. Rasko. 2021. "Splice and Dice: Intronic microRNAs, Splicing and Cancer" Biomedicines 9, no. 9: 1268. https://doi.org/10.3390/biomedicines9091268