PMID:23226399

Citation	Hassan, F, Nuovo, GJ, Crawford, M, Boyaka, PN, Kirkby, S, Nana-Sinkam, SP and Cormet-Boyaka, E (2012) MiR-101 and miR-144 regulate the expression of the CFTR chloride channel in the lung. PLoS ONE 7:e50837
Abstract	The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that plays a critical role in the lung by maintaining fluid homeostasis. Absence or malfunction of CFTR leads to Cystic Fibrosis, a disease characterized by chronic infection and inflammation. We recently reported that air pollutants such as cigarette smoke and cadmium negatively regulate the expression of CFTR by affecting several steps in the biogenesis of CFTR protein. MicroRNAs (miRNAs) have recently received a great deal of attention as both biomarkers and therapeutics due to their ability to regulate multiple genes. Here, we show that cigarette smoke and cadmium up-regulate the expression of two miRNAs (miR-101 and miR-144) that are predicted to target CFTR in human bronchial epithelial cells. When premature miR-101 and miR-144 were transfected in human airway epithelial cells, they directly targeted the CFTR 3'UTR and suppressed the expression of the CFTR protein. Since miR-101 was highly up-regulated by cigarette smoke in vitro, we investigated whether such increase also occurred in vivo. Mice exposed to cigarette smoke for 4 weeks demonstrated an up-regulation of miR-101 and suppression of CFTR protein in their lungs. Finally, we show that miR-101 is highly expressed in lung samples from patients with severe chronic obstructive pulmonary disease (COPD) when compared to control patients. Taken together, these results suggest that chronic cigarette smoking up-regulates miR-101 and that this miRNA could contribute to suppression of CFTR in the lungs of COPD patients.
Links	PubMed PMC3511328 Online version:10.1371/journal.pone.0050837
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:CFTR		GO:0030324: lung development	ECO:0000314:		P		Cigarette smoke can lead to the over regulation of MiR-101. MiR-101 is one of the proteins that is responsible for regulating the CFTR protein chloride channels in the lungs. The CFTR chloride channel is responsible for carrying chloride ions across the membrane. Mutations of the chloride channel can cause mucous to accumulate on the membrane which is a sign of cystic fibrosis. Figure 6 shows that MiR-101 is up regulated in is COPD patients with histories of smoking. The up regulation in COPD patients with a history of smoking showed great suppression in the CFTR protein.	complete CACAO 6422

References

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