Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P33527 (
ABCC1
)
1,164
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Chemoresistance is often developed in small cell lung cancer (SCLC) patients and leads to poor prognosis. Hox genes, a highly conserved family, play a crucial role in apoptosis, receptor signalling and differentiation. MicroRNAs (miRNAs) have also been shown to play a crucial role in these biological processes by regulating the target genes. Several studies reported that both Hox genes and miRNAs are involved in chemoresistance. The aim of our study is to characterise the clinical significance and functional roles of
HOXA1
in SCLC. Expression of
HOXA1
was examined in 63 cases of SCLC tissues and 29 cases of blood by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) methods. Multivariate analysis confirmed the prognostic significance of
HOXA1
in SCLC patients. Restoration of
HOXA1
expression was carried out in SCLC multidrug resistant
cell line H69AR
and its parental cell line H69 to assess its influence on chemoresistance. Luciferase reporter assay was used to assess
HOXA1
as a target of miR-100. The results showed that
HOXA1
was expressed in 46% (29/63) of SCLC. Low
HOXA1
expression was associated with the poor prognosis of SCLC (P<0.05 by the Fisher's Exact Test) and the shorter survival rate (P<0.001 by the Kaplan-Meier method).
HOXA1
expression on both mRNA and protein levels significantly correlated with chemotherapy response. Enforced expression of
HOXA1
in resistant H69AR cells led to increased chemosensitivity through increasing cell apoptosis and cell-cycle arrest. Inhibition of
HOXA1
expression using
HOXA1
siRNA in H69 cells resulted in cell resistance to therapeutic drugs through reducing drug-induced cell apoptosis accompanied with cell cycle arrest. Expression of endogenous miR-100 was significantly elevated in resistant H69AR cells and negatively related with
HOXA1
expression. The expression of
HOXA1
in SCLC tissues correlated inversely with the expression levels of miR-100. Reporter assays confirmed that miR-100 targeted predicted sites in 3'-untranslated region (3'-UTR) of
HOXA1
gene. Our data suggested that
HOXA1
-mediated SCLC chemoresistance is under the regulation of miR-100.
HOXA1
may be a prognostic predictor and potential therapeutic target in human SCLC.
...
PMID:Downregulation of HOXA1 gene affects small cell lung cancer cell survival and chemoresistance under the regulation of miR-100. 2455 85
