Background: Radio- and chemotherapy (RT/CT) resistance hampers success in combating small and non-small cell lung cancers (SCLC/NSCLC). The underlying molecular mechanisms of RT/CT resistance of LCs are multifactorial and have been understood in part hitherto. miRNAs, key regulators of mRNAs, are well-recognised oncomirs; however, their role in regulating RT response remains poorly understood.
Methods: Six human NSCLC and five SCLC cell lines with different SF2 values were investigated. Using microarray we examined whether expression of miRNAs is linked to the RT resistance of NSCLCs or SCLCs. Obtained data were validated by quantitative real-time PCR. Apoptosis and senescence were analysed using siRNA transfection, western blot and flow cytometry.
Results: miRNA-21, miRNA-1827, miRNA-214, miRNA-339-5p, miRNA-625, miRNA-768-3p, miRNA-523-3p, miRNA-1227, miRNA-324-5p, miRNA-423-3p, miRNA-1301 and miRNA-1249 are differentially expressed in LC cells. miRNA-214 is upregulated in RT-resistant NSCLC cells relative to radiosensitive counterparts. Considering miRNA-214 as a putative regulator of RT resistance, we demonstrate that knockdown of miRNA-214 in radioresistant NSCLCs sensitised them to RT by stimulation of senescence. Consistently, overexpression of miRNA-214 in radiosensitive NSCLCs protected against RT-induced apoptosis. Protection was mediated by p38MAPK, as downregulation of this kinase could reverse the miRNA-214 overexpression-induced resistance of NSCLC cells.
Conclusion: miRNA profiling of LC revealed putative RT resistance signalling circuits, which might help in sensitisation of LC to RT.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494421 | PMC |
| http://dx.doi.org/10.1038/bjc.2012.382 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Insights into NEK2 inhibitors as antitumor agents: From mechanisms to potential therapeutics.
Eur J Med Chem
January 2025
Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Healthand, Department of Frontiers Science Center for Disease-related Molecular Network, Core Facilities, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. Electronic address:
NEK2, a serine/threonine protein kinase, is integral to mitotic events such as centrosome duplication and separation, microtubule stabilization, spindle assembly checkpoint, and kinetochore attachment. However, NEK2 overexpression leads to centrosome amplification and chromosomal instability, which are significantly associated with various malignancies, including liver, breast, and non-small cell lung cancer. This overexpression could facilitate tumor development and confer resistance to therapy by promoting aberrant cell division and centrosome amplification.
View Article and Find Full Text PDFNegative prognostic significance of primary cilia and cytoplasmic β-catenin expression in non-small cell lung cancer.
Neoplasma
December 2024
Department of Oncology, First Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czech Republic.
The objective of this study was to investigate the prognostic significance of the frequency of primary cilia (PC) and β-catenin expression in 218 patients (pts) with non-small cell lung cancer (NSCLC), including 125 pts with adenocarcinoma and 93 pts with squamous cell carcinoma. In the whole group of 218 pts with NSCLC, overall survival (OS) was significantly inferior among pts with present PC than without PC (p=0.024) and with higher cytoplasmic β-catenin expression (25-75%) than with lower cytoplasmic β-catenin expression (<25%) (p=0.
View Article and Find Full Text PDFMethylation status of selected genes in non-small cell lung carcinoma - current knowledge and future perspectives.
Neoplasma
December 2024
Department of Clinical and Molecular Pathology and Medical Genetics, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
DNA methylation is recognized as an early event in cancer initiation and progression. This review aimed to compare the methylation status of promoter regions in selected genes across different histological subtypes of non-small cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and the rare but highly aggressive large-cell neuroendocrine carcinoma (LCNEC). A comprehensive literature search was conducted in the PubMed database until August 17, 2024, using standardized keywords to identify reports on promoter methylation in NSCLC.
View Article and Find Full Text PDFCircular RNA ATP9A Stimulates Non-small Cell Lung Cancer Progression via MicroRNA-582-3p/Ribosomal Protein Large P0 Axis and Activating Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathway.
Appl Biochem Biotechnol
January 2025
Department of Oncology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No.71 Baoshan North Road, Yunyan District, Guiyang City, 550001, Guizhou Province, China.
Circular RNAs (circRNAs), along with their pathogenic property in non-small cell lung cancer (NSCLC), require comprehensive analyses and explanations. The study is established with the purpose to elucidate the potential molecular mechanism of circATP9A in NSCLC. CircATP9A and microRNA (miR)-582-3p were evaluated by real-time quantitative polymerase chain reaction, and ribosomal protein large P0 (RPLP0), cleaved caspase-3, cleaved Ki-67, epithelial-to-mesenchymal transition (EMT)-associated proteins (N-cadherin and E-cadherin), and core proteins of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were by Western blot.
View Article and Find Full Text PDFDesign, synthesis and antitumour activity of pyrimidine derivatives as novel selective EGFR kinase inhibitors.
Mol Divers
January 2025
School of Pharmacy, Shandong Second Medical University, Weifang, 261053, Shandong, People's Republic of China.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, often linked to overexpression or abnormal activation of the epidermal growth factor receptor (EGFR). The issue of developing resistance to third-generation EGFR kinase inhibitors, such as osimertinib, underscores the urgent need for new therapies to overcome this resistance. Our findings revealed that compound A8 exhibits 88.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!