MicroRNA in the Diagnosis and Treatment of Doxorubicin-Induced Cardiotoxicity

Figures

• 

  Figure 1. Schematic diagram of synthesis and processing of miRNAs. The gene of the miRNA is transcribed into a pri-miRNA under the mediation of RNA polymerase II/III and then cut into the pri-miRNA by DROSHA; subsequently, the pre-miRNA is transported by exportin-5 into the cytoplasm and cleaved by the endonuclease DICER; then, under the action of helicase, two single strands are formed, one of which forms RISC with AGO, and the other is degraded.

• 

  Figure 2. Mechanism diagram of DIC. Five potential mechanisms by which DOX acts on the cardiovascular system and produces cardiotoxicity: oxidative stress; the role of topoisomerase in DIC; DNA methylation; cardiac progenitor cells; endoplasmic reticulum stress.

• 

  Figure 3. Schematic diagram of the occurrence and development of oxidative stress in DIC. DOX enters the body and produces ROS mainly through the following ways, mediating oxidative stress; DOX combines with eNOS to induce DOX, generating ROS; DOX binds to the inner mitochondrial membrane to form complexes, alters cardiolipin function, and produces ROS; DOX forms Fe-DOX complexes with Fe, which contribute to ROS production; under the action of the NOX enzyme, DOX reacts with NADPH to generate ROS; DOXOL, a metabolite of DOX, inhibits the sodium-calcium exchange channel, causing an imbalance in the level of Ca2+ in the cell, and produces ROS, which inhibits CaMKII and aggravates the imbalance of Ca2+ level; excessive consumption of antioxidants; downregulation of Nrf2 pathway expression; DOX treatment significantly inhibited SIRT1 deacetylase activity and protein levels, and promoted deubiquitination of p53 and activation of caspase-3. The above seven ways are involved in DOX-induced oxidative stress, individually or synergistically.