Early-life origin of prostate cancer through deregulation of miR-206 networks in maternally malnourished offspring rats

Abstract

Abstract The Developmental Origins of Health and Disease (DOHaD) concept has provided the framework to assess how early life experiences can shape health and disease throughout the life course. While maternal malnutrition has been proposed as a risk factor for the developmental programming of prostate cancer (PCa), the molecular mechanisms remain poorly understood. Here, we found an association between deregulation of steroidogenesis and impairment of the ventral prostate (VP) growth in young offspring rats exposed to maternal low protein diet (LPD) during gestation and lactation. Reanalysis of RNA-seq data demonstrated that miR-206 was upregulated in the VP of young maternally malnourished offspring. Target prediction and in vitro studies identified Plasminogen (PLG) as a direct target of miR-206. To give further insights into the participation of the miR-206-PLG network in prostate carcinogenesis in the progeny submitted to maternal LPD. RT-qPCR analysis revealed deregulation of the miR-206-PLG network in the VP of older rats that developed prostate carcinoma in situ. Furthermore, mimic studies revealed a negative correlation between miR-206 and estrogen receptor α (ESR1) expression in PNT2 cells. Together, we demonstrate that early life estrogenization associated with deregulation of miR-206-networks can contribute to the developmental origins of PCa in maternally malnourished offspring. Understanding the molecular mechanisms by which early life malnutrition affects offspring health can encourage the adoption of a governmental policy for the prevention of non-communicable chronic diseases related to the DOHaD concept.