Affiliations: [a] Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria | [b] BioTechMed-Graz, Graz, Austria | [c] Division of Transplantation Surgery, Department of Surgery, Medical University of Graz, Graz, Austria | [d] Ludwig Boltzmann Institute for Lung Vascular Research, Medical University of Graz, Graz, Austria
Correspondence:
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Corresponding author: Andelko Hrzenjak, Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria. Tel.: +43 31638573860; E-mail: [email protected].
Abstract: BACKGROUND: The potential of microRNAs (miRNAs) as molecular tumor biomarkers for early diagnosis and prognosis in lung cancer is still unclear. OBJECTIVE: To analyze expression of miRNAs in A549 lung adenocarcinoma (LUAD) cells and in primary, non-malignant bronchial epithelial (BE) cells from healthy donors. To analyze the most prominently deregulated miRNAs in plasma samples of LUAD patients and healthy donors. MATERIALS AND METHODS: The expression of 752 miRNAs in LUAD and BE cells was assessed by RT-qPCR with mean-centering restricted normalization. The relative plasma levels of 18 miRNAs in LUAD patients and healthy donors were analyzed using RT-qPCR and normalized to miR-191-5p and miR-16-3p. Putative interactions between miRNAs and their target genes were investigated in silico. RESULTS: Out of 752 miRNAs, 37 miRNAs were significantly deregulated in A549 cells compared to BE cells. MiR-15b-3p, miR-148a-3p, miR-193b-3p, and miR-195-5p were significantly deregulated in plasma samples of LUAD patients compared to donors. The target genes of those four miRNAs are involved in essential mechanisms in cancer development and progression. CONCLUSIONS: There are substantial differences between cancer and control miRNA expression in vitro and in plasma samples of LUAD patients compared to healthy donors. Four deregulated miRNAs are promising as a diagnostic biomarker for adenocarcinoma of the lung.
