Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Seidl, C; Panzitt, K; Bertsch, A; Brcic, L; Schein, S; Mack, M; Leithner, K; Prinz, F; Olschewski, H; Kornmueller, K; Hrzenjak, A.
MicroRNA-182-5p regulates hedgehog signaling pathway and chemosensitivity of cisplatin-resistant lung adenocarcinoma cells via targeting GLI2.
Cancer Lett. 2020; 469: 266-276.
Doi: 10.1016/j.canlet.2019.10.044
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Hrzenjak Andelko
- Panzitt Katrin
- Seidl Carina
- Co-Autor*innen der Med Uni Graz
- Birnstingl Alexandra
- Brcic Luka
- Kornmüller Karin
- Leithner Katharina
- Mack Maximilian
- Olschewski Horst
- Prinz Felix
- Schein Sandra
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- Abstract:
- Lung cancer is one of the deadliest cancers worldwide. Late diagnosis at an advanced, inoperable stage makes chemotherapy a treatment of choice, yet, with low response rates. The hedgehog signaling pathway (HHSP) is often reactivated in cancer. We identified miR-182-5p as a regulator of GLI2, a transcriptional regulator of the HHSP, and explored the role of the miR-182-5p/GLI2 axis in carcinogenesis and cisplatin resistance of lung adenocarcinoma (LADC). Expression of miRNAs and target genes was analyzed by RT-qPCR, expression of the GLI-protein family in LADC and adjacent lung tissue (n = 27 pairs) by immunohistochemistry. MiR-182-5p was manipulated, and data were generated by immunoblotting, immunofluorescence, apoptosis, proliferation/viability, dual-luciferase-, and colony forming assays. MiR-182-5p was down-regulated in cisplatin-resistant LADC cells and directly targeted GLI2. Interference with miR-182-5p or GLI2 silencing resulted in modulation of cell proliferation, clonogenic potential, and cisplatin-sensitivity. HHSP was markedly reactivated in LADC tissue compared to adjacent non-malignant lung tissue. Our results indicate that the miR-182-5p/GLI2 axis modulates tumorigenesis and cisplatin-resistance in LADC cells, by influencing the HHSP. Therefore, this axis might be considered as a potential biomarker and future therapeutic target in LADC patients. Copyright © 2019 Elsevier B.V. All rights reserved.
- Find related publications in this database (Keywords)
- Lung adenocarcinoma
- miRNA
- Cisplatin
- Hedgehog signaling pathway
- Chemoresistance