MiR-34a/c-Dependent PDGFR-α/β Downregulation Inhibits Tumorigenesis and Enhances TRAIL-Induced Apoptosis in Lung Cancer.

Abstract

Lung cancer is the leading cause of cancer mortality in the world today. Although some advances in lung cancer therapy have been made, patient survival is still poor. MicroRNAs (miRNAs) can act as oncogenes or tumor-suppressor genes in human malignancy. The miR-34 family consists of tumor-suppressive miRNAs, and its reduced expression has been reported in various cancers, including non-small cell lung cancer (NSCLC). In this study, we found that miR-34a and miR-34c target platelet-derived growth factor receptor alpha and beta (PDGFR-α and PDGFR-β), cell surface tyrosine kinase receptors that induce proliferation, migration and invasion in cancer. MiR-34a and miR-34c were downregulated in lung tumors compared to normal tissues. Moreover, we identified an inverse correlation between PDGFR-α/β and miR-34a/c expression in lung tumor samples. Finally, miR-34a/c overexpression or downregulation of PDGFR-α/β by siRNAs, strongly augmented the response to TNF-related apoptosis inducing ligand (TRAIL) while reducing migratory and invasive capacity of NSCLC cells.

• Authors: Michela Garofalo, Young-Jun Jeon, Gerard J Nuovo, Justin Middleton, Paola Secchiero, Pooja Joshi, Hansjuerg Alder, Natalya Nazaryan, Gianpiero Di Leva, Giulia Romano, Melissa Crawford, Patrick Nana-Sinkam, Carlo M Croce
• Journal: PloS one (PLoS One) Vol. 8 Issue 6 Pg. e67581 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23805317 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)

Chemical References

• 3' Untranslated Regions
• MIRN34 microRNA, human
• MicroRNAs
• RNA, Messenger
• RNA, Small Interfering
• TNF-Related Apoptosis-Inducing Ligand
• Receptor, Platelet-Derived Growth Factor alpha
• Receptor, Platelet-Derived Growth Factor beta

Topics

• 3' Untranslated Regions
• Apoptosis (drug effects)
• Base Sequence
• Carcinogenesis (drug effects)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation (drug effects)
• Down-Regulation (drug effects)
• Humans
• Lung (metabolism, pathology)
• Lung Neoplasms (metabolism, pathology)
• MicroRNAs (genetics, metabolism)
• RNA Interference
• RNA, Messenger (metabolism)
• RNA, Small Interfering (metabolism)
• Receptor, Platelet-Derived Growth Factor alpha (antagonists & inhibitors, genetics, metabolism)
• Receptor, Platelet-Derived Growth Factor beta (antagonists & inhibitors, genetics, metabolism)
• Sequence Alignment
• TNF-Related Apoptosis-Inducing Ligand (toxicity)