title: miR-20a regulates expression of the iron exporter ferroportin in lung cancer.
abstract: Ferroportin (FPN) exports iron from duodenal enterocytes, macrophages, and hepatocytes to maintain systemic iron homeostasis. In addition, FPN is expressed in various cancer cells. Here, we show that in lung cancer, FPN expression is regulated by miR-20a. Within the FPN-3'-untranslated region (3'UTR), we identify and experimentally validate three evolutionarily conserved target sites for the microRNA (miRNA) members of the miR-17 seed family, including miR-20a. Our analysis of RNA sequencing data from patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) revealed that FPN messenger RNA (mRNA) levels are significantly decreased in tumor compared to matched healthy tissue, while miR-20a levels are increased. A significant negative correlation of miR-20a and FPN expression was observed. Functional studies further demonstrate that FPN is post-transcriptionally regulated by miR-20a in non-small cell lung cancer (NSCLC) cells and that overexpression or knockdown of miR-20a or FPN affects NSCLC proliferation and colony formation. Taken together, our data suggest that increased expression of miR-20 in lung cancer may decrease iron export, leading to intracellular iron retention, which, in turn, favors cell proliferation.
  
  
  CONCLUSIONS
  miR-20a controls expression of the iron exporter ferroportin (FPN) by binding to highly conserved target sites in its 3'UTR. Expression of miR-20a is inversely correlated to FPN in lung cancer. Low FPN expression stimulates proliferation and colony formation of non-small cell lung cancer (NSCLC) cells, possibly by increasing iron availability for cancer cell proliferation.
authors.affiliation: Department of Pediatric Hematology, Oncology, and Immunology, University of Heidelberg, Heidelberg, Germany.|Molecular Medicine Partnership Unit, University of Heidelberg, Heidelberg, Germany.
authors.forename: Kamesh R
authors.initials: KR
authors.lastname: Babu
authors.affiliation: Department of Pediatric Hematology, Oncology, and Immunology, University of Heidelberg, Heidelberg, Germany. Martina.Muckenthaler@med.uni-heidelberg.de.|Molecular Medicine Partnership Unit, University of Heidelberg, Heidelberg, Germany. Martina.Muckenthaler@med.uni-heidelberg.de.
authors.forename: Martina U
authors.initials: MU
authors.lastname: Muckenthaler
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D027682:Cation Transport Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017124:Conserved Sequence; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D000098742:Ferroportin
chemical_list: D020413:3' Untranslated Regions; D027682:Cation Transport Proteins; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; D000098742:Ferroportin
keywords: Colony formation; Ferroportin; Lung cancer; Proliferation; miR-20a