Decreased expression of microRNA-199b increases protein levels of SET (protein phosphatase 2A inhibitor) in human choriocarcinoma

Received 1 January 2009; received in revised form 13 May 2009; accepted 9 October 2009. published online 09 November 2009.
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Abstract

We compared microRNA profiles between choriocarcinoma and non-cancerous trophoblasts, and revealed that miR-199b was underexpressed in choriocarcinoma. By computational prediction and microarray studies, SET (protein phosphatase 2A inhibitor) was shown to be one of the target genes regulated by miR-199b. Ectopic expression of miR-199b inhibited endogenous SET protein levels and the activity of the luciferase reporter containing the 3′-UTR of SET. Further comparisons of formalin-fixed paraffin-embedded human choriocarcinoma, mole, and non-cancer trophoblast tissues confirmed the initial findings of low miR-199b expression and SET upregulation in choriocarcinomas, suggesting that microRNA-dysregulated SET protein may account for the rapid growth seen with choriocarcinomas.

Keywords: Choriocarcinoma, Gestation, MicroRNA, Mole, Placenta

a Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taiwan

b Department of Clinical Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taiwan

c Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taiwan

d Department of Biotechnology, Ming-Chuan University, Taiwan

e Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taiwan

Corresponding authors. Address: Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taiwan. Tel.: +886 3 3281200; fax: +886 3 3288252 (T.-H. Wang).

1 Both authors contributed equally to this study.

PII: S0304-3835(09)00627-2

doi:10.1016/j.canlet.2009.10.005