OP0020 Aberrant mirna expression in paclitaxel-spared lung adenocarcinoma-initiating cells from the A549 cell line

• Published in: European journal of cancer (1990) Vol. 50; p. e7
• Main Authors: Chen, Z.T, Lin, S, Sun, J.G, Ma, H, Yao, Q, Zhang, A.-M, Peng, L.N
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.05.2014
• Subjects: Hematology, Oncology and Palliative Medicine
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2014.03.038

Background Non-small-cell lung cancer (NSCLC) is a leading cause of tumour mortality. Increasing evidence reveals that most tumour cells contain a rare subpopulation of cells, termed tumour-initiating cells (TICs), that are thought to be the main cause of tumour relapse and metastasis. Further studies indicate that miRNAs are involved in the dysregulation of TICs in various tumours and can serve as oncogenes or tumour suppressors in tumorigenesis and tumour progression. Thus, improved recognition of aberrant miRNAs in lung TICs might help to explain the potential mechanism of lung cancer biobehaviour. This study aimed to investigate miRNA expression in lung adenocarcinoma-initiating cells. Methods We obtained lung adenocarcinoma-initiating cells from the A549 cell line based on paclitaxel treatment combined with serum-free cultivation miRNA expression in TICs. Control A549 cells were investigated by microarray. Quantitative RT-PCR was done to validate the array data. Findings Inverse-induction combined with paclitaxel treatment induced a CD133+/CD326+ subpopulation from the A549 cell line. By in vitro and in vivo experiments, features of stemness were found in the CD133+/CD326+ cells, including self-renewal, differentiation, high expression of genes associated with cancer stem cells, and stronger capability for tumorigenesis. CD133+/CD326+ cells were found in primary lung adenocarcinoma tissue by immunofluorescence. Compared with control A549 cells, 50 aberrant miRNAs were found in the CD133+/CD326+ subpopulation with microRNA array, involving different regulation of lung cancer biobehaviour, such as tumorigenesis, invasion, chemoresistance and radioresistance, and epithelial–mesenchymal transition. Of ten chosen representative miRNAs, the expression trend of six miRNAs was found to be consist with array data by quantitative RT-PCR. Interpretation From the A549 cell line, lung adenocarcinoma-initiating cells marked with CD133+/CD326+ were effectively enriched with paclitaxel treatment combined with serum-free cultivation. With aberrant miRNA expression, the lung adenocarcinoma-initiating cells might play an important part in pathogenesis of NSCLC.