title: Hu/elav RNA-binding protein HuR regulates parathyroid hormone related peptide expression in human lung adenocarcinoma cells.
abstract: In 54 stage I and II human lung adenocarcinomas, HuR and PTHrP levels were positively correlated and the PTHrP-HuR status of the tumor was an independent prognostic marker of the clinical outcomes of patients. The possibility that HuR could upregulate PTHrP expression in lung adenocarcinoma was investigated by immunohistochemical, Western blot and RT-PCR analyses in HCC44 and DV90 human lung adenocarcinoma cell lines. In both cell lines, knockdown of HuR by specific siRNAs reduced PTHrP mRNAs and both cellular and secreted protein. Moreover, it inhibited cell growth and induced cell apoptosis, as revealed by the increase of caspase-3 activity. These effects were partially rescued by the addition of exogenous PTHrP (1-34). Analysis by actinomycin D assay revealed that in both cell lines HuR silencing produced a decrease of PTHrP mRNA half-life by about 70%. These findings add PTHrP to the list of lung cancer-associated genes, whose mRNA is stabilized by HuR.
authors.affiliation: Institute of Pathologic Anatomy, Università Cattolica del S. Cuore, Roma, Italy.
authors.forename: Libero
authors.initials: L
authors.lastname: Lauriola
authors.forename: Simona
authors.initials: S
authors.lastname: Serini
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Granone
authors.forename: Paola
authors.initials: P
authors.lastname: Lanza
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.forename: Gabriella
authors.initials: G
authors.lastname: Calviello
authors.forename: Franco Oreste
authors.initials: FO
authors.lastname: Ranelletti
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D051959:ELAV Proteins / Q000378:metabolism*; D000067780:ELAV-Like Protein 1; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C054296:parathyroid hormone-related protein (1-34)