TY - JOUR
T1 - Role of aquaporin-5 in gallbladder carcinoma
AU - Sekine, S.
AU - Shimada, Y.
AU - Nagata, T.
AU - Sawada, S.
AU - Yoshioka, I.
AU - Matsui, K.
AU - Moriyama, M.
AU - Omura, T.
AU - Osawa, S.
AU - Shibuya, K.
AU - Hashimoto, I.
AU - Watanabe, T.
AU - Hojo, S.
AU - Hori, R.
AU - Okumura, T.
AU - Yoshida, T.
AU - Tsukada, K.
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
KW - Aquaporin
KW - Gallbladder carcinoma
KW - Gemcitabine
KW - Immunohistochemistry
KW - Phosphatase and tensin homolog
KW - Tissue microarray
UR - http://www.scopus.com/inward/record.url?scp=84894450480&partnerID=8YFLogxK
U2 - 10.1159/000355675
DO - 10.1159/000355675
M3 - 学術論文
C2 - 24217644
AN - SCOPUS:84894450480
SN - 0014-312X
VL - 51
SP - 108
EP - 117
JO - European Surgical Research
JF - European Surgical Research
IS - 3-4
ER -