Review Article
Advances in Understanding Mitochondrial MicroRNAs (mitomiRs) on the Pathogenesis of Triple-Negative Breast Cancer (TNBC)
Table 4
Roles and mechanisms of mitomiRs in mitochondrial homeostasis on dynamics, mitophagy, calcium transport, and mtDNA maintenance.
| mitomiR | Function | Target gene | Mechanism of action | Outcome | PMID | Reference |
| Mitochondrial dynamics | miR-195 | (-)TNBC | MFN2 | ↓MFN2 ↓OPA1 ↑DRP1 | ↑Mitochondrial fission ↓OCR ↓Mitochondrial ATP ↑ROS ↑Apoptosis | 30932749 | Purohit et al., 2019 [70] | Mitophagy | miR-137 | (+)BCSC | FUNDC1 | ↓FUNDC1/↓NIX/↓LC3-II →↓Mitophagy | ↑Mitochondrial biogenesis ↓ROS ↑ATP production ↓Apoptosis | 32945512 | Hu et al., 2020 [72] | miR-1 | (-)BCSC | MINOS1 GPD2 LRPPRC | ↓MINOS1/↓GPD2/↓LRPPRC →↑Disorganized cristae →↑PINK1→↑LC3-II →↑Mitophagy | Cell cycle arrest at G0/G1 ↓Tumor growth | 31765945 | Zhang et al., 2019 [71] | Mitochondrial calcium transport | miR-4488 | (-)TNBC | CX3CL1 | ↓MCU (TNBC)→ ↑miR-4488 EVs (TNBC)→ ↓CX3CL1 (ECs) | ↓Angiogenesis ↓Tumor metastasis ↑Survival time of mice | 33067576 | Zheng et al., 2020 [74] | miR-340 | (-)TNBC | MCU | ↓MCU→↓[Ca2+]m →↓LDH | ↓Glucose uptake ↓ATP production ↓Lactate production ↓Migration ↓Tumor metastasis | 29137386 | Yu et al., 2017 [37] | miR-195 | (-)TNBC | CYP27b1 | ↑[Ca2+]m ↑[Ca2+]C ↓ΔΨm | ↓EMT ↓Proliferation ↓Migration ↓Invasion | 26632252 | Singh et al., 2015 [43] | mtDNA maintenance | miR-499a | (+)TNBCSC | POLB | ↑POLB→↑mtDNA stability | ↑Tumorigenic genes ↑CSC genes ↑Proliferation | 33278391 | Manda et al., 2020 [76] | miR-128 | (-)TNBC | INSR, IRS1 | ↓INSR/↓INS1→↓mtDNA content | ↓Mitochondrial bioenergetics ↓Proliferation ↓Tumor growth | 29116653 | Xiao et al., 2018 [33] | miR-199a | (-)TNBC | TFAM | ↓TFAM→↓mtDNA content | ↑Cisplatin-induced apoptosis ↓Proliferation | 28126676 | Fan et al., 2017 [75] | miR-4485 | (-)TNBC | 16S rRNA | ↓16S rRNA→↓ETC enzyme activity→↓mitochondrial ATP | ↑Cell death ↓Proliferation ↓Tumor growth | 28220193 | Sripada et al., 2017 [44] |
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(+): oncogenic; (-): tumor suppressor; “↑”: enhanced; “↓”: reduced; ΔΨm: mitochondrial membrane potential; BCSC: breast cancer stem cell; ↑[Ca2+]C: cytosolic calcium; [Ca2+]m: mitochondrial calcium; CX3CL1: C-X3-C motif chemokine ligand 1; CYP27B1: cytochrome P450 family 27, subfamily B, polypeptide 1; DRP1: dynamin-related protein 1; ECs: endothelial cells; EVs: extracellular vesicles; FUNDC1: FUN14 domain containing 1; GPD2: glycerol-3-phosphate dehydrogenase 2; INSR: insulin receptor; IRS1: insulin receptor substrate 1; LC3: microtubule-associated proteins 1A/1B light chain 3B; LDH: lactate dehydrogenase; LRPPRC: leucine-rich pentatricopeptide-repeat containing; MCU: mitochondrial calcium uniporter; MFN: mitofusin; MINOS1: mitochondrial inner membrane organizing system 1; NIX: NIP-3-like protein X; OPA1: optic atrophy 1; PINK1: PTEN-induced kinase 1; POLB: DNA polymerase beta; ROS: reactive oxygen species; TFAM: mitochondrial transcription factor A; UQCC2: ubiquinol-cytochrome C reductase core protein 2.
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