xCT as a potential marker for neuroendocrine cells in high-risk prostate cancer and the relation to AL122023.1-miR-26a/30d/30e axis

Abstract

Purpose Prostate cancer is the second most common type of cancer in male worldwide. Stromal-epithelial interaction is thought to have a major impact on cancer development and progression. Interaction via soluble factors previously revealed a reduction in the expression of xCT and AL122023.1 in prostate carcinoma cells LNCaP after seven days of co-culture with stromal primary p21 cells. Furthermore, xCT is known to be a putative target for miR-26a, miR-30d and miR-30e which in turn potentially interact with the lncRNA AL122023.1. Methods We validated the repression of xCT and AL122023.1 at RNA level by quantitative real-time PCR and at protein level by Western Blotting. The lncRNA-miRNA-interaction was analyzed by luciferase reporter assays whereas the localization and distribution of xCT in prostate tissue of different developmental stages was evaluated by immunostaining. Results The interaction between AL122023.1 and miR-26a/-30d/-30e was verified and further investigated at protein level regarding xCT. An indirect inhibitory effect of AL122023.1 on the xCT expression could be shown, but miR-26a/-30d/-30e caused no inhibition. Moreover, immunostaining displayed a precise xCT expression in neuroendocrine cells ranging from fetal, healthy juvenile and adult prostate tissue to benign prostatic hyperplasia and finally advanced prostate cancer. Conclusion This study explores the relevance and function of xCT and AL122023.1 in the prostate and exposes xCT as a potential marker or therapeutic target in high-risk prostate cancer.