Fig. 2

Abnormal transmembrane transport. The SLC31A1, SLC22A1/2/3, as members of SLC superfamily, are significant transporters in charge of drug inflow. Downregulation of SLC transporters reduce platinum uptake, leading to chemoresistance in ovarian cancer. The role of miRNA in SLC expression lacks sufficient evidence. The ABC transporter family include ABCB1, ABCG2, ABCC1, which are responsible for drug efflux and then reduce intracellular concentration of platinum. miR130a/b, miR-186, miR-495 can directly bind with the 3'-UTR of ABCB1 mRNA or regulate PTEN, XIPA, and PI3K, leading to decreased ABCB1 transcription or translation level. miR-21-5p and miR-212-3p also have a regulatory factor of ABCB1 and ABCG2, respectively. miR-185-5p, miR-326, miR-508-3p and miR-134 can regulate the expression of ABCC1. ATP7A/7B are another contributor of drug efflux. miR-139 can directly bind to the 3'-UTR of ATP7A/7B, leading to apoptosis induction and increasing the chemosensitivity of ovarian cancer. MT can bind to cisplatin and deactivates it, which decreases drug efficacy and induces drug resistance. GST catalyzes glutathione to bind platinum and causes drug inactivation, which is associated with platinum resistance in ovarian cancer. (SLC, solute carrier superfamily; GST, Glutathione transferase; MT, Metallothionein)