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Investigation of lncRNA H19 in prostate cancer cells and secreted exosomes upon androgen stimulation or androgen receptor blockage

OBJECTIVES:

In the present study, cellular or exosomal expression of H19, an oncofetal lncRNA gene, was evaluated during androgen stimulation via dihydrotestosterone (DHT) or AR blockage via enzalutamide in cultured hormone-sensitive Pca cells which overexpres AR (LNCaP-AR+).

BACKGROUND:

Prostate cancer (PCa) is an androgen-dependent disease. Androgen receptor (AR) antagonists (i.e. enzalutamide) have been used for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). Exosomes and their contents (non-coding RNA) play an important role in tumor development and progression.

METHODS:

Cells were treated with DHT (10 nM) and/or enzalutamide (10 uM) for 24 h. Cellular and exosomal expression of H19 was investigated using a quantitative polymerase chain reaction assay.

RESULTS:

Our findings reveal that cellular H19 expression decreased approximately 2.3fold in mean upon androgen stimulation of Pca cells. AR blockage using enzalutamide restored DHT effect and we found increased H19 expression (≤ 2.5-fold, p < 0.05) upon the combined use of DHT and enzalutamide compared to control cells. Similar to its cellular effect, DHT treatment also led to declined exosomal expression of H19 (≤ 3-fold, p < 0.0001). Restorative effect of enzalutamide on decreased H19 expression induced by androgen stimulation was not observed in exosomes.

CONCLUSION:

This experimental study provides evidence that H19 might be involved in androgen receptor pathway. Further research is needed to explore the role of H19 in Pca and intercellular communication via exosomes (Fig. 2, Ref. 32).

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S1250 Enzalutamide (MDV3100) Enzalutamide (MDV3100) is an androgen-receptor (AR) antagonist with IC50 of 36 nM in LNCaP cells. Enzalutamide is shown to increase autophagy. (373) (4)

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