Fishing „the miRNA“ in order to target drug-induced epithelial-mesenchymal transition in ovarian cancer
Anamaria Brozović, dr.sc.
+385 1 456 1145
Although the majority of women with advanced ovarian cancer respond to first-line chemotherapy, most responses are not long-lasting. The fact that ovarian cancer is mostly diagnosed late when it is already metastasized and developed cross-resistance to the drugs, makes its treatment unsuccessful.
Epithelial-mesenchymal transition (EMT) is a biological process that allows a polarized epithelial cell, which normally interacts with basement membrane via its basal surface, to undergo multiple biochemical changes that enable it to acquire a mesenchymal cell phenotype. Among others, EMT is involved in tumour metastasis. The hallmark of EMT is a loss of the epithelial marker E-cadherin and gain of mesenchymal markers such as vimentin and/or fibronectin.
MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level. They bind to complementary sequences located on target RNA transcripts, resulting in gene silencing as a consequence of target RNA cleavage, degradation or translational repression. Because they are involved in regulation of many targets they are recognized as master regulators of entire biological pathways. E-cadherin and other EMT regulators are the main targets of miRNAs. Besides Zeb1/2, which are the main targets of the miRNA-200 family, other miRNAs such as miR-10, miR-155, miR-7, miR-221/222 are described to be involved in EMT as well.
Despite all accumulated knowledge about the mechanisms of EMT development and tumour resistance to drugs, the role of EMT in tumour response to the therapy is not completely understood as well as which signalling pathway(s) link EMT and drug resistance. This cooperation is focused on detection of miRNAs, which are linking those two phenomena, with a goal to gain more knowledge about possible new targets for future therapy of ovarian cancer.