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

Abstract

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.

Alternatively Constructed Estrogen Receptor Alpha-Driven Super-Enhancers Result in Similar Gene Expression in Breast and Endometrial Cell Lines

“…All TF families that had their motifs enriched at the sites bound by ERα identified in Ishikawa cells were previously directly associated with ERα in endometrial cancer [38]. TEA domain transcription factor 4 (TEAD4) cooperates with activator protein 1 (AP-1) in the chromatin of endometrial cancer cells and establishes an interaction between ERα and progesterone receptor (PR) in breast cancer cells [39,40], transcription factor 12 (TCF12), also known as HEB, functions as an oncogene as well as a tumor suppressor in several human cancer types [41]. In mouse experiments, TCF12 was also identified as a key prognostic factor for endometrial cancer [42].…”

TCF12 promotes the tumorigenesis and metastasis of hepatocellular carcinoma via upregulation of CXCR4 expression

“…In breast cancer, TCF12 mediated the activation of cancer-associated fibroblasts (CAFs) and contributed to extracellular matrix (ECM) remodeling, triggering the invasion and metastasis of breast cancer cells both in vitro and in vivo 17. In contrast, other studies revealed that TCF12 mediated suppressor activities and was drastically downregulated in oral squamous cell carcinoma and prostate cancer 18, 19. Nevertheless, the function and molecular mechanism of TCF12 in HCC have never been reported until now.…”

Liquid Biopsy-Based Exo-oncomiRNAs Can Predict Prostate Cancer Aggressiveness

“…As a target of miR-221, TCF12 has been related to survival after diagnosis of colon cancer [ 55 ], and there is evidence to suggest that TCF12 is involved in cell migration and differentiation [ 56 ]. Interestingly, the status of TCF12 has been found to be an independent predictor of biochemical recurrence-free survival in PCa [ 57 ]. We show here that miR-221-3p likely regulates TCF12 in PC-3 cells and its expression is, in turn, regulated by sTWEAK.…”

“…Our studied patient cohort comprised 97 consecutive patients with PCa who had undergone radical prostatectomy by open surgery at the University Hospital Joan XXIII, Tarragona, between 2015 and 2019—laparoscopic or robotic surgery (intraperitoneal or extraperitoneal—with or without bilateral ilio-obturator lymphadenectomy, according to the estimated risk of lymphadenopathy based on the Briganti nomogram [ 56 ]. Patients were stratified according to the 2014 ISUP-GG and TNM classification [ 57 , 58 ]. Patients were stratified into two categories: low-risk (ISUP Group I and II) and high-risk (ISUP Groups III, IV and V).…”