Background: Primate-specific melanoma antigen-A11 (MAGE-A11) increases steroid receptor transcriptional activity and enhances prostate cancer cell growth. Results: MAGE-A11 activates E2F1 by interacting with retinoblastoma-related protein p107. Conclusion: MAGE-A11 influences cell cycle regulatory pathways in a molecular hub for transcription. Significance: MAGE-A11 is a proto-oncogene whose increased expression impacts multiple signaling mechanisms that contribute to prostate cancer growth and progression.

Background: Melanoma antigen-A11 (MAGE-A11) is a primate-specific steroid receptor coregulator. Results: MAGE-A11 mediates the stimulatory effects of cyclic AMP on androgen receptor (AR) transcriptional activity in prostate cancer and can rescue transcriptional activity of complementary inactive AR mutants. Conclusion: MAGE-A11 increases AR transcriptional activity by linking AR dimers. Significance: MAGE-A11 is a new target for prostate cancer treatment.

Antisense long noncoding RNAs (lncRNAs) are reported to play a regulating role in carcinogenesis of various human malignancies. However, the function of lncRNAs and their underlying mechanism in renal cell carcinoma (RCC) is still unknown. The aims of this study are to investigate the expression of lncRNA BX357664 in RCC and to explore its function in RCC cell lines. As a result, BX357664 was downregulated in RCC according to previous microarray analysis and qualitative real-time polymerase chain reaction. After the upregulation of BX357664, reduced migration, invasion, and proliferation capabilities in RCC cells were detected. Furthermore, Western blot analysis was conducted to identify the influence of BX357664 on epithelialto-mesenchymal transition, matrix metalloproteinase 2, matrix metalloproteinase 9, and transforming growth factor-beta 1 (TGF-β1)/p38/HSP27 signaling pathway in RCC. Subsequently, upregulating the protein level of TGF-β1 in the presence of BX357664 could rescue the suppression of the malignant behavior mediated by BX357664, indicating that BX357664 attributed its inhibitory role to the suppression of TGF-β1. Therefore, we investigated a novel lncRNA BX357664, which might exhibit its inhibitory role in RCC metastasis and progression by blocking the TGF-β1/p38/ HSP27 pathway.

Male sex development and growth occur in response to high affinity androgen binding to the androgen receptor (AR). In contrast to complete amino acid sequence conservation in the AR DNA and ligand binding domains among mammals, a primate-specific difference in the AR NH 2 -terminal region that regulates the NH 2 -and carboxyl-terminal (N/C) interaction enables direct binding to melanoma antigen-A11 (MAGE-11), an AR coregulator that is also primate-specific. Human, mouse, and rat AR share the same NH 2 -terminal 23 FQNLF 27 sequence that mediates the androgen-dependent N/C interaction. However, the mouse and rat AR FXXLF motif is flanked by Ala 33 that evolved to Val 33 in primates. Human AR Val 33 was required to interact directly with MAGE-11 and for the inhibitory effect of the AR N/C interaction on activation function 2 that was relieved by MAGE-11. The functional importance of MAGE-11 was indicated by decreased human AR regulation of an androgen-dependent endogenous gene using lentivirus short hairpin RNAs and by the greater transcriptional strength of human compared with mouse AR. MAGE-11 increased progesterone and glucocorticoid receptor activity independently of binding an FXXLF motif by interacting with p300 and p160 coactivators. We conclude that the coevolution of the AR NH 2 -terminal sequence and MAGE-11 expression among primates provides increased regulatory control over activation domain dominance. Primate-specific expression of MAGE-11 results in greater steroid receptor transcriptional activity through direct interactions with the human AR FXXLF motif region and indirectly through steroid receptor-associated p300 and p160 coactivators.

The evolutionarily conserved genes that encode the tripartite motif (TRIM) protein family are involved in various biological processes, including cellular immunity, inflammatory reaction, antiviral activity, and tumor progression. One member of this protein family, Trim59, has been reported as a novel biomarker for the occurrence and progression of multiple human carcinomas, such as lung cancer, gastric cancer, cervical cancer, and osteosarcoma. However, little is known about the relationship between Trim59 and bladder carcinogenesis. In this study, we examined the expression of Trim59 in bladder cancer (Bca) specimens and cell lines, and investigated its biological roles in Bca cell lines. We found that Trim59 was upregulated in Bca tissues and cell lines. In addition, using transwell chamber assays and the cell scratch test, we determined that knockdown of Trim59 significantly inhibited the epithelial-mesenchymal transition (EMT) and the processes of cell invasion and migration in Bca cell lines. Furthermore, we found that downregulated Trim59 expression could also inhibit cell proliferation and promote apoptosis. As a result, we demonstrated that the effects of Trim59-induced EMT and invasion/migration in Bca cells were achieved by the activation of the transforming growth factor beta/Smad2/3 signaling pathway. Our findings also revealed that Trim59 can present oncogenic activity, and may serve as a novel candidate target for bladder carcinoma treatment.

The aberrant expression of microRNAs (miRs) has been identified to serve a crucial role in tumor progression. The present study aimed to evaluate the role of miR-126 in human prostate cancer (PCa). Firstly, miR-126 expression in prostate cancer tissues and cell lines was analyzed. A luciferase reporter assay and a rescue assay were performed, which identified ADAM metalloproteinase domain 9 (ADAM9) as the target gene of miR-126. Subsequently, Kaplan-Meier and log-rank analyses were used to investigate the association between ADAM9 expression and PCa prognosis. The results revealed that miR-126 expression was significantly downregulated in PCa tissues and cell lines. miR-126 overexpression was demonstrated to reduce PCa cell proliferation and metastasis, and to reverse the epithelial-mesenchymal transition process in vitro. In addition, as the target gene of miR-126, the upregulation of ADAM9 reestablished cell functions, including cell proliferation, migration and invasion. Patients with high ADAM9 expression levels exhibited a shorter biochemical recurrence-free survival time. In summary, miR-126 serves a role in the proliferation and metastasis of PCa cells, indicating that miR-126 and ADAM9 may represent potential biomarkers in the progression of advanced PCa, in addition to therapeutic targets.

Recent studies have shown that matrix metalloproteinases (MMPs) might be a biomarker for predicting outcomes of bladder cancer. However, the prognostic value of overexpression of MMPs in bladder cancer is debatable and the studies are inconsistent. Therefore, this meta-analysis was performed to clarify the specific association and prognostic value of overexpression of MMPs in bladder carcinoma. Relevant studies were identified by searching PubMed, EMBASE, and the Web of Science. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for disease-specific survival (DSS), overall survival (OS), disease/recurrence-free survival (DFS/RFS), and progression/metastasis-free survival (PFS/MFS) were analyzed to determine the prognostic value of MMPs. In total, eighteen applicable studies were included in this meta-analysis. We found that high expression of MMPs significantly correlated with a poor DSS and OS (HR=1.66; 95% CI = 1.38–2.01 and HR= 1.67; 95%CI= 1.26–2.22). MMPs also predicted tumor progression and metastasis with a pooled HR of 3.03 (95% CI 1.98–4.64). However, high MMPs expression had no pivotal impact on DFS/RFS (HR= 1.21; 95% CI= 0.96–1.53). With the purpose of better understanding the prognostic role of MMPs in patients wirh bladder carcinoma, we carried out this systematic review and meta-analysis.

Background: Progesterone regulates the cyclic function of the human endometrium through its receptors and coregulatory proteins. Results: Primate-specific melanoma antigen-A11 (MAGE-11) interacts with the human progesterone receptor-B (PR-B) unique NH 2 -terminal region to coregulate progesterone-dependent gene activation. Conclusion: MAGE-11 is an isoform-specific coregulator of human PR-B. Significance: PR-B and progesterone regulation of human endometrium requires a primate-specific steroid receptor coregulator.