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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