BAG3 increases the invasiveness of uterine corpus carcinoma cells by suppressing miR-29b and enhancing MMP2 expression.
Approximately 30% of uterine corpus carcinomas are diagnosed at an advanced stage and have a poor prognosis. Our previous study indicated that BCL2-associated athanogene 3 (BAG3) enhances matrix metalloproteinase-2 (MMP2) expression and binds to MMP2 to positively regulate the process of cell invasion in ovarian cancer cells. Recently, altered miRNA expression patterns were observed in several groups of patients with endometrial cancers. One of the altered miRNAs, miR-29b, reportedly reduces tumor invasiveness by suppressing MMP2 expression. Our aim in the present study was to examine the relationships among BAG3, miR-29b and MMP2 in endometrioid adenocarcinoma cells. We found that BAG3 suppresses miR-29b expression and enhances MMP2 expression, which in turn increases cell motility and invasiveness. Moreover, restoration of miR-29b through BAG3 knockdown reduced MMP2 expression, as well as cell motility and invasiveness. Collectively, our findings indicate that BAG3 enhances MMP2 expression by suppressing miR-29b, thereby increasing the metastatic potential of endometrioid adenocarcinomas.
Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan.
Shutaro
S
Habata
Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan.
Masahiro
M
Iwasaki
Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan.
Asuka
A
Sugio
Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan.
Miwa
M
Suzuki
Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan.
Masato
M
Tamate
Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan.
Seiro
S
Satohisa
Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan.
Ryoichi
R
Tanaka
Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan.
Tsuyoshi
T
Saito
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2