A key hallmark of cancer cells is their altered metabolism, known as Warburg effect. Lactate dehydrogenase A (LDHA) executes the final step of aerobic glycolysis and has been reported to be involved in the tumor progression. However, the function of LDHA in prostate cancer has not been studied. In current study, we observed overexpression of LDHA in the clinical prostate cancer samples compared with benign prostate hyperplasia tissues as demonstrated by immunohistochemistry and real-time qPCR. Attenuated expression of LDHA by siRNA or inhibition of LDHA activities by FX11 inhibited cell proliferation, migration, invasion, and promoted cell apoptosis of PC-3 and DU145 cells. Mechanistically, decreased Warburg effect as demonstrated by reduced glucose consumption and lactate secretion and reduced expression of MMP-9, PLAU, and cathepsin B were found after LDHA knockdown or FX11 treatment in PC-3 and DU145 cells. Taken together, our study revealed the oncogenic role of LDHA in prostate cancer and suggested that LDHA might be a potential therapeutic target.

Over the years, it has become increasingly clear that males and females respond differently towards environmental stressors, highlighting the importance of including both sexes when studying the effects of stress. This study aims to provide further insight into the detailed consequences of exposing female mice to 21 days of chronic social defeat stress (CSDS). We used a protocol that relies on the ability of odorants and pheromones in male urine to trigger male mouse aggressive behavior. Collected male C57Bl/6n urine was applied to female C57Bl/6n mice who were then attacked by a novel male CD1 mouse each day according to the CDSD protocol. Control females were pair-housed and handled daily. Physiological, neuroendocrine and behavioral changes were evaluated during the experiment. CSDS exposure resulted in number of physiological changes, such as body weight gain, enlarged adrenals and reduced thymus weight, exaggerated HPA-axis negative feedback and increased anxiety-like behavior. However, no generalized social avoidance behavior was observed. This study provides important insights in the physiological, neuroendocrine and behavioral responses of female mice to CSDS, which are partially dependent on estrous cycle stage. This protocol will allow direct comparison of male and female responses to CSDS and enable sex-specific study of mechanisms underlying individual stress resilience.

for their excellent technical assistant and support. We thank Stefanie Unkmeir, Sabrina Bauer and the scientific core unit Genetically Engineered Mouse Models for genotyping support. We also thank Jessica Keverne for language editing the manuscript. The graphical abstract was created with Biorender.com

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