FBI-1 and AMPK in choriocarcinoma cells

Abstract

Choriocarcinoma is a rare and highly aggressive tumorwhich belongs to the gestational trophoblastic diseases (GTD). It can be originated from either gestational or non-gestational origins. Choriocarcinoma is characterized by biphasic pattern and is composed of a mixed population of mononuclear cytotrophoblasts and multinucleated syncytotrophoblasts. Because of its low prevalence, information on the biology of choriocarcinoma is still insufficient. FBI-1 is an oncogenic transcription factor that is found to be overexpressed in various cancers. In our previous study, overexpression of FBI-1 in gestational choriocarcinoma cell lines,JEG-3 and JAR, were found. FBI-1 affects cell survival through regulating apoptosis and modulating cell motility in choriocarcinoma cells. However, the underlying mechanisms on how FBI-1affectscellular functions is largely unknown. AMPK is a master regulator in metabolic pathways and helps cells to maintain energy homeostasis in response to stressful conditions. Dysregulation on AMPK upsets the balance in metabolism that may play a role in the pathogenesis of cancers. Besides, AMPK is strongly associated with Warburg effect which is considered as a hallmark of cancer. In this study, we aim to investigate the relation between FBI-1 and AMPK in choriocarcinoma. Normal trophoblast cell lines HTR-8/SVneo and TEV-1as well as choriocarcinoma cell lines JAR, BeWo and JEG-3 were used. Levels of mRNA and protein expressions were evaluated by qRT-PCR and western blot respectively. In choriocarcinoma cell lines, relative lower levels of both AMPKα1 andα2 mRNA and protein were demonstrated when compared with the normal trophoblast cells lines. After knock down of FBI-1 in choriocarcinoma cell lines,JEG-3 and JAR, the expression of AMPK α1 but not theα2 subunit was suppressed. The expressions of a panel of glycolysis-related genes, including hexokinase II (HK2), phosphoglycerate kinase 1 (PGK1), lactate dehydrogenase A (LDHA), pyruvate kinase muscle isozymeM2 (PKM2), aldolase C (ALDOC) and glucose transporter 1(GLUT1), were examined in this study. It was found that the expressions of most of these genes were unaffected. ALDOC mRNA and HK2 protein expression was found to decrease in choriocarcinoma cells with FBI-1 knockdown, suggesting that glycolytic pathway was affected by FBI-1. These results tend to indicate that AMPK may cooperate with FBI-1 in choriocarcinoma cells to gain survival advantages through modulation of glycolysis although further study is needed.