Identifikation YAP/TAZ-regulierter nicht-kodierender RNAs (ncRNAs) im Leberkrebs
Zusammenfassung der Projektergebnisse
Body fluids from cancer patients are informative regarding conditions in tumor tissues. Thus, biomarkers detected by liquid biopsy can guide clinicians in designing personalized therapies and may serve as a proxy for treatment success. However, biomarkers that predict the existence of druggable target structures cannot be reliably defined in blood samples due to genetic tumor heterogeneity and molecules released from non-tumorous cells. To illustrate the applicability of RNA signatures as cancer-spanning biomarkers, we investigated expression data from hepatocellular carcinoma (HCC) and lung adenocarcinoma (LUAD) cells after genetic silencing of Hippo pathway effectors. Using a machine learning algorithm, a 4 gene long non-coding RNA (lncRNA) signature consisting of CYTOR, MIR4435- 2HG, SNHG1, and SNHG17 is defined that correlates with the nuclear abundance of the oncogene yes-associated protein (YAP) and its activity in cancer cells. Evaluation of human cancer expression data illustrate that the lncRNA signature is a robust predictor for YAP activity in several tumor types. YAP transcriptionally controls signature lncRNAs, which themselves support tumor cell progression via tumor cell-intrinsic mechanisms. lncRNAs are overexpressed in YAPS127A transgenic mouse livers as well as in a subgroup of human cancer tissues and serum samples. Importantly, YAP accumulation in human HCC tissues is significantly associated with lncRNA signature abundance in the serum of these patients. Lastly Liquid biopsy-based detection of pan-cancer lncRNA signatures defines the activity of transcriptional regulators such as YAP in tumor cells. We conclude, that serum lncRNA signatures can serve as valuable tools for diagnostics, therapy design, as well as for monitoring treatment success.
Projektbezogene Publikationen (Auswahl)
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Methylation in MIRLET7A3 Gene Induces the Expression of IGF-II and Its mRNA Binding Proteins IGF2BP-2 and 3 in Hepatocellular Carcinoma. Frontiers in Physiology, 9.
Waly, Amr A.; El-Ekiaby, Nada; Assal, Reem A.; Abdelrahman, Mohamed M.; Hosny, Karim A.; El Tayebi, Hend M.; Esmat, Gamal; Breuhahn, Kai & Abdelaziz, Ahmed I.
