TY - JOUR
T1 - Hu/elav RNA-binding protein HuR regulates parathyroid hormone related peptide expression in human lung adenocarcinoma cells
AU - Lauriola, Libero
AU - Serini, Simona
AU - Granone, Pierluigi
AU - Lanza, Paola
AU - Martini, Maurizio
AU - Calviello, Gabriella
AU - Ranelletti, Franco Oreste
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Human lung adenocarcinoma, HuR expression, HuR knockdown, PTHrP expression, PTHrP mRNA stability, human lung adenocarcinoma cell lines
KW - Human lung adenocarcinoma, HuR expression, HuR knockdown, PTHrP expression, PTHrP mRNA stability, human lung adenocarcinoma cell lines
UR - http://hdl.handle.net/10807/52809
M3 - Article
SN - 0309-0167
SP - 1205
EP - 1216
JO - Histopathology
JF - Histopathology
ER -