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

Figure 1

Graphic overview depicting the roles of mitomiRs in modulating mitochondrial homeostasis and its involvements in the scenario of TNBC progression. (a) TNBC stages classified by TNM system [7]. Advanced breast cancer comprises inoperable locally advanced breast cancer and metastatic (stage IV) breast cancer. The bone, the liver, and the lungs account, respectively, for about 67%, 40.8%, and 36.9% of the common metastatic sites, wherein basal-like BC (BLBC, accounting for 75% of the TNBC subtypes [6]) hits 40%, 35%, and 35%, respectively, of the metastatic BC [7]. (b) The mitomiR biogenesis and its impacts on mitochondrial dimensions. The precursor transcripts (pri-miR) are transcribed and posttranscriptionally cleaved by microprocessor (DROSHA and DGCR8) in the nucleus to liberate the pre-miR hairpin. The pre-miR is then exported to the cytoplasm by exportin 5 (XPO5) bound to guanosine 5-triphosphate (Ran-GTP). In the cytoplasm, the DICER endoribonuclease cleaves the loop of the pre-miR to produce the mature miR. The resulting miR embeds in a groove of Argonaute (AGO) of the RNA-induced silencing complex (RISC) and ultimately targets a strand of mRNA by base pairing its 3 untranslated region (UTR). When bound to an mRNA, RISC inhibits translation, yet the main effect is to degrade the mRNA through deadenylation. mitomiRs are a particular cluster of miRs that predominantly occupy a sphere of influence on dimensions of mitochondrial homeostasis, including metabolic reprogramming, redox homeostasis, mitochondrial quality control, mtDNA maintenance, and Ca²⁺ balance.