Role of aquaporin-5 in gallbladder carcinoma.
OBJECTIVE
Aquaporins (AQPs) are important in controlling bile formation. However, the exact role in human gallbladder carcinogenesis has not yet been defined.


METHODS
AQP-5-expressing gallbladder carcinoma (GBC) cell lines (NOZ) were transfected with anti-AQP-5 small interfering RNA (siRNA). Growth, migration, invasion assay, and drug susceptibility tests were performed. Next, microRNA (miRNA) expression was analyzed by miRNA oligo chip (3D-Gene®). AQP-5 and AQP-5-related miRNA target gene expressions were also analyzed using tissue microarray (TMA) in 44 GBC samples.


RESULTS
Treatment with AQP-5 siRNA decreased cell proliferation, migration, and invasion. On the other hand, those cells increased IC50 of gemcitabine. By performing miRNA assays, miR-29b, -200a, and -21 were shown to be highly overexpressed in cells treated with AQP-5 siRNA NOZ. When focusing on miR-21, phosphatase and tensin homolog (PTEN) was found to be a target of miR-21. In the TMA, AQP-5/PTEN coexpression was significantly associated with the depth of invasion and MIB-1 index (p = 0.003, 0.010). Survival of patients with a high AQP-5/PTEN coexpression was longer than that of patients with a low coexpression (p = 0.003).


CONCLUSIONS
Our result suggested that miR-21 and PTEN may contribute to the role of AQP-5 in GBC. AQP-5 and PTEN cascades are favorable biomarkers of GBC.
Department of Surgery and Science, University of Toyama, Toyama, Japan.
S
S
Sekine
Y
Y
Shimada
T
T
Nagata
S
S
Sawada
I
I
Yoshioka
K
K
Matsui
M
M
Moriyama
T
T
Omura
S
S
Osawa
K
K
Shibuya
I
I
Hashimoto
T
T
Watanabe
S
S
Hojo
R
R
Hori
T
T
Okumura
T
T
Yoshida
K
K
Tsukada
D000328:Adult; D000368:Aged; D051402:Aquaporin 5 / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D005706:Gallbladder Neoplasms / Q000209:etiology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D046888:Tissue Array Analysis
C496036:AQP5 protein, human; D051402:Aquaporin 5; D035683:MicroRNAs; D012333:RNA, Messenger; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human