Advances in Understanding Mitochondrial MicroRNAs (mitomiRs) on the Pathogenesis of Triple-Negative Breast Cancer (TNBC)

Table 2

Roles and mechanisms of mitomiRs in the perturbation of redox homeostasis.

mitomiR	Function	Target gene	Mechanism of action	Outcome	PMID	Reference
miR-34a	(-)TNBC	BCL-2	↓BCL-2/↑BAX; →↑ROS/↓ΔΨm	↓Mammosphere formation; ↓Tumor growth	32319481	Ahir et al., 2020 [54]
miR-27a	(-)TNBC	SLC7A11; CTH; NFE2L2	↓xCT, ↓CTH, ↓NRF2; →↑ROS, ↓autophagic flux	↓Mammosphere formation; ↓CSC markers; ↑TNBC sensitivity to doxorubicin and paclitaxel	32066826	Ueda et al., 2020 [36]
miR-324	(-)TNBC	ACK1	↓ACK1→↑ROS→; ↑DNA oxidative damage	↓Proliferation; ↓Tumor growth	31751910	Zhang et al., 2019 [52]
miR-4485	(-)TNBC	16S rRNA	↓16S rRNA→↓ETC enzyme activity→↑ROS/↓ΔΨm	↑Cell death; ↓Proliferation; ↓Tumor growth	28220193	Sripada et al., 2017 [44]
let-7a	(-)TNBC	SCD	↓SCD→↑OCR→↑ROS	↑SOD2, TXNRD1, HO-1; ↓Proliferation; ↑Cell cycle arrest; ↑TNBC sensitivity to doxorubicin	25669981	Serguienko et al., 2015 [42]
miR-373	(+)TNBC	TXNIP	↓TXNIP→↑TRX→↓ROS→↑HIF-1α→↑TWIST; 1→↑miR-373	↑EMT; ↑Migration and invasion; ↑Tumor growth; ↑Tumor metastasis	26196741	Chen et al., 2015 [53]
miR-200a	(-)TNBC	KEAP1	↓KEAP1→nuclear translocation of NRF2→↑NQO1	↑Antioxidant pathway; ↓Anchorage-independent cell growth	21926171	Eades et al., 2011 [51]

(+): oncogenic; (-): tumor suppressor; “↑”: enhanced; “↓”: reduced; ΔΨm: mitochondrial membrane potential; ACK1: activated CDC42 kinase 1; BAX: Bcl-2-associated X protein; BCL-2: B cell lymphoma 2; CTH: cystathionine gamma-lyase; CSCs: cancer stem cells; ETC: electron transport chain; HAX-1: HCLS1-associated protein X-1; HO-1: heme oxygenase 1; NQO1: NAD(P)H quinone dehydrogenase 1; NRF2 (encoded by NFE2L2): nuclear factor erythroid 2-related factor 2; ROS: reactive oxygen species; SCD: stearoyl-CoA desaturase; SOD2: superoxide dismutase mitochondrial; TRAIL: tumor necrosis factor-related apoptosis-inducing ligand; TNBCSC: triple-negative breast cancer stem cell; TRX: thioredoxin; TWIST1: twist family BHLH transcription factor 1; TXNIP: thioredoxin-interacting protein; TXNRD1: thioredoxin reductase 1; xCT (encoded by SLC7A11): cystine/glutamate transporter.