Decreased expression of TCF12 contributes to progression and predicts biochemical recurrence in patients with prostate cancer.

As a member of helix-loop-helix protein family, transcription factor 12 functions as either an oncogene or a tumor suppressor in various human cancers. However, there are no reports on its involvement in prostate cancer. To investigate clinical relevance of transcription factor 12 in prostate cancer and to evaluate its roles in malignant phenotypes of this cancer in vitro and in vivo, we here examined expression patterns of transcription factor 12 protein in 50 prostate cancer tissue specimens by immunohistochemistry. Then, associations of transcription factor 12 expression with various clinicopathological characteristics and patients' prognosis of prostate cancer were evaluated. Its involvements in cancer cell proliferation, migration, invasion, and tumor growth were determined by in vitro and in vivo experiments. As a result, the positive immunostaining of transcription factor 12 protein was localized in cytoplasm and/or nucleus of prostate cancer cells. Its expression levels were decreased with prostate cancer Gleason score increased. Statistically, the decreased expression of transcription factor 12 protein more frequently occurred in prostate cancer patients with high Gleason score, positive metastasis, prostate-specific antigen failure, and short biochemical recurrence-free survival (all p < 0.05). Importantly, multivariate analysis showed that the status of transcription factor 12 expression was an independent predictor of biochemical recurrence-free survival in prostate cancer. Functionally, enforced expression of transcription factor 12 suppressed cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. In conclusion, transcription factor 12 protein may be a novel molecule which plays a critical role in prostate cancer progression and patients' prognosis, suggesting it might be a promising therapeutic target for prostate cancer therapy.

Mitochondrion-associated protein peroxiredoxin 3 promotes benign prostatic hyperplasia through autophagy suppression and pyroptosis activation.

Benign prostatic hyperplasia (BPH) is one of the most common diseases in the senior men and age plays an important role in the initiation and development of BPH. Mammalian cells primarily use the autophagy-lysosome system to degrade misfolded/aggregated proteins and dysfunctional organelles such as mitochondria and suppress pyroptosis, a type of cell death that stimulates inflammatory responses and growth of other cells around. Peroxiredoxin 3 (PRDX3) is the only mitochondrion-associated member of peroxiredoxin family enzymes that exert their protective antioxidant role in cells through their peroxidase activity. We hypothesized that PRDX3 may inhibit autophagy to activate pyroptosis to induce growth of prostatic epithelial cells. Here we show that PRDX3 maintained the integrity of mitochondria and its depletion led to an enhancement of oxidative stresses. PRDX3-associated and PRDX3-free mitochondria co-existed in the same cells. PRDX3 expressed at higher levels in prostatic epithelial cells in prostate tissues from BPH patients and BPH-representative cell line than in prostate tissues from healthy donors and a cell line representing normal epithelial cells. PRDX3 suppressed autophagy flux and activated pyroptosis to induce inflammatory responses and stimulate the over-growth of prostate tissues. Therefore, higher levels of PDRX3 in prostatic epithelial cells may promote the initiation and development of BPH through autophagy inhibition and pyroptosis activation.