Role of proteins HMGB1 and HMGB2 in the malignancy of cells from surface epithelium of the ovary and study of relevant sequences for the interactions with IncRNAs

Resumo

Ovarian cancer (OC) is one of the most common types of cancer amongwomen in the world. The main problem in the diagnosis of OC is that the initialeffects are silent with respect to the perception by patients, so that a high number ofcases detected already correspond to an advanced stage of the disease in whichtherapeutic intervention is less successful. resulting in high mortality. Dysregulationof HMGB1 and HMGB2 in cancer cells can lead to sustained proliferative signaling,resistance to cell death, tumor-promoted inflammation, dysregulation of cellularenergetics, invasion, metastasis, and stimulation of angiogenesis. On the other hand,long non-coding RNAs (lncRNAs), which do not encode proteins, but haveregulatory functions of gene expression at different levels, affect all processesrelated to carcinogenesis such as the cell cycle, differentiation, proliferation,apoptosis and tumorigenesis. In this work we have studied in vitro the interactionsof the HMGB1 and HMGB2 proteins with lncRNAs previously associated withovarian cancer, trying to know the domains of the proteins and the sequences oflncRNAs that are necessary for the interaction, which may contribute to thediscovery of new therapeutic targets. We have also studied how knocking out theHMGB1 and HMGB2 genes modifies specific functions in healthy and cancerousovarian cells. Finally, we have purified extracellular vesicles from the original linesand the mutants (knockouts) and have analyzed their effect on the malignancy ofovarian epithelial cells in primary culture. The results obtained allow a greaterknowledge of the cellular processes related to ovarian cancer in which the HMGB1 and HMGB2 proteins intervene.