Cancer research (Chicago, Ill.), 2014-09, Vol.74 (17), p.4720-4730
2014
Details
- Autor(en) / Beteiligte
- Titel
- IL-1β-Mediated Repression of microRNA-101 Is Crucial for Inflammation-Promoted Lung Tumorigenesis
- Ist Teil von
- Cancer research (Chicago, Ill.), 2014-09, Vol.74 (17), p.4720-4730
- Ort / Verlag
- Philadelphia, PA: American Association for Cancer Research
- Erscheinungsjahr
- 2014
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Inflammatory stimuli clearly contribute to lung cancer development and progression, but the underlying pathogenic mechanisms are not fully understood. We found that the proinflammatory cytokine IL-1β is dramatically elevated in the serum of patients with non-small cell lung cancer (NSCLC). In vitro studies showed that IL-1β promoted the proliferation and migration of NSCLC cells. Mechanistically, IL-1β acted through the COX2-HIF1α pathway to repress the expression of microRNA-101 (miR-101), a microRNA with an established role in tumor suppression. Lin28B was identified as critical effector target of miR-101 with its repression of Lin28B, a critical aspect of tumor suppression. Overall, IL-1β upregulated Lin28B by downregulating miR-101. Interestingly, cyclooxygenase-2 inhibition by aspirin or celecoxib abrogated IL-1β-mediated repression of miR-101 and IL-1β-mediated activation of Lin28B along with their stimulatory effects on NSCLC cell proliferation and migration. Together, our findings defined an IL-1β-miR-101-Lin28B pathway as a novel regulatory axis of pathogenic inflammatory signaling in NSCLC.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0008-5472eISSN: 1538-7445DOI: 10.1158/0008-5472.CAN-14-0960Titel-ID: cdi_proquest_miscellaneous_1819140999
- Format
- –
- Schlagworte
- Animals, Antineoplastic agents, Biological and medical sciences, Carcinogenesis - genetics, Carcinogenesis - metabolism, Carcinogenesis - pathology, Carcinoma, Non-Small-Cell Lung - genetics, Carcinoma, Non-Small-Cell Lung - metabolism, Carcinoma, Non-Small-Cell Lung - pathology, Cell Line, Cell Line, Tumor, Cell Movement - genetics, Cell Proliferation - genetics, Cyclooxygenase 2 - genetics, Cyclooxygenase 2 - metabolism, Down-Regulation - genetics, HEK293 Cells, Humans, Hypoxia-Inducible Factor 1, alpha Subunit - genetics, Hypoxia-Inducible Factor 1, alpha Subunit - metabolism, Inflammation - genetics, Inflammation - metabolism, Inflammation - pathology, Interleukin-1beta - genetics, Interleukin-1beta - metabolism, Lung Neoplasms - genetics, Lung Neoplasms - metabolism, Lung Neoplasms - pathology, Male, Medical sciences, Mice, Mice, Inbred BALB C, Mice, Nude, MicroRNAs - genetics, Pharmacology. Drug treatments, Signal Transduction - genetics, Tumors, Up-Regulation - genetics