Tripartite motif 44 (TRIM44), a member of the TRIM protein family, has been shown to play a role in tumor development and progression. However, the potential involvement of TRIM44 in prostate cancer has not been fully explored. Therefore, in the present study, we analyzed the expression of TRIM44 in prostate cancer and assessed the role of TRIM44 in the progression of prostate cancer. Our results showed that the expression of TRIM44 was significantly upregulated in human prostate cancer cell lines. In addition, knockdown of TRIM44 significantly inhibited the proliferation, migration, and invasion of prostate cancer cells in vitro, as well as attenuated the tumor growth in vivo. Mechanistic studies showed that knockdown of TRIM44 significantly reduced the levels of phosphorylated PI3K and Akt in PC-3 cells. In conclusion, this study provided evidence that knockdown of TRIM44 inhibited proliferation and invasion in prostate cancer cells, at least in part, through the inactivation of the PI3K/Akt signaling pathway. These results suggest that TRIM44 may be a potential therapeutic target for the treatment of prostate cancer.

No abstract

Despite accumulating evidence suggesting a critical role of signal transducer and activator of transcription 3 (STAT3) and Survivin in human bladder cancer, the effects of silencing these genes on the proliferation of T24 bladder carcinoma cells remain unknown. Here, we investigated the inhibitory effects of STAT3 or Survivin silencing on the in vitro and in vivo growth of human T24 bladder carcinoma cells. Small interfering RNA (siRNA) vectors targeting STAT3, Survivin, or both genes were designed and synthesized. The recombinant plasmid DNA constructs were confirmed by DNA sequencing. They were then transiently transfected into T24 cells, and the mRNA and protein expressions of STAT3 and Survivin were determined using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot, respectively. Cell proliferation was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The in vivo growth-inhibition effects of the siRNA vectors were assessed using a bladder cancer mouse model. The tumor weight and size was recorded 4 weeks post-inoculation. We successfully synthesized four siRNA vectors targeting STAT3 and four vectors targeting Survivin. The STAT3-3 and Survivin-4 siRNA constructs were most efficient in reducing STAT3 or Survivin expression, respectively. We then constructed a vector containing these two sequences together (STAT3-Survivin siRNA) and found that the single vector efficiently silenced STAT3 and Survivin expression. Moreover, silencing of STAT3 or Survivin significantly suppressed the in vitro and in vivo proliferation of T24 cells compared to the controls (P<0.05). Our findings indicated that the downregulation of STAT3 or Survivin can suppress the proliferation of T24 bladder cancer cells. Moreover, no additive effects were observed when STAT3 and Survivin were knocked down together, suggesting that they work in the same signaling pathway in T24 cells. These results provide valuable insights into understanding the pathways involved during the tumorigenesis of bladder cancer.

Background: Bladder cancer (BCa) has the highest incidence of aggressive malignant tumors in the urogenital system and is the ninth most common cancer worldwide. Immune function-related genes (IFRGs), which are plentiful in immune cells and the immune microenvironment (IME), have the potential to assess prognosis and predict the efficacy of immunotherapy. A complete and significant immunogenomic analysis based on abundant BCa genetic samples from The Cancer Genome Atlas (TCGA) will provide insight into the field. Results: A total of 57 differentially expressed IFRGs were significantly associated with the clinical outcomes of patients with BCa. Functional enrichment analysis showed that these genes actively participated in the KEGG pathway of human cytomegalovirus infection. Based on the IFRGs (CALR, MMP9, PAEP, RBP7, STAT1, CACYBP, ANHAK, RAC3, SLIT2, EDNRA, IGF1, NAMPT, NTF3, PPY, ADRB2 and SH3BP2), the risk scores were calculated to predict survival and reveal the relationships with age, sex, grade, staging, T-stage, N-stage, and M-stage. Interestingly, IFRG-based risk scores (IRRSs) reflected the infiltration of several types of immune cells. The expression of CACYBP was more significant in grade 3, T3 and T4 stages than in earlier grades and T-stages. Conclusion: Our results highlighted some sIFRGs with remarkable clinical relevance, showed the driving factors of the immune repertoire, and illustrated the significance of IFRG-based individual immune features in the identification, monitoring, and prognosis of patients with BCa. Methods: Based on the TCGA dataset, we integrated the expression profiles of IFRGs and overall survival (OS) in 430 patients with BCa. Differentially expressed IFRGs and survival-related IFRGs (sIFRGs) were highlighted by calculating the difference algorithm and COX regression analysis in patients with BCa. Based on computational biology, the potential molecular mechanisms and characteristics of these IFRGs were also explored. Using multivariate Cox analysis, new risk scores based on immune-related genes were developed. The expression of CACYBP was verified by qPCR, western blot and immunohistochemistry. The relations between CACYBP and clinical features were proven by immunohistochemistry.

Ulinastatin [or called as urinary trypsin inhibitor (UTI)] plays a role in regulating neurological deficits evoked by transient cerebral ischemia. However, the underlying mechanisms still need to be determined. The present study was to examine the effects of UTI on autophagy, Nrf2-ARE and apoptosis signal pathway in the hippocampus in the process of neurological functions after cerebral ischemia using a rat model of cardiac arrest (CA). CA was induced by asphyxia followed by cardiopulmonary resuscitation (CPR) in rats. Western blot analysis was employed to determine the expression of representative autophagy (namely, Atg5, LC3, Beclin 1), p62 protein (a maker of autophagic flux), and Nrf2-ARE pathways. Neuronal apoptosis was assessed by determining expression levels of Caspase-3 and Caspase-9, and by examining terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL). The modified neurological severity score (mNSS) and spatial working memory performance were used to assess neurological deficiencies in CA rats. Our results show that CA amplified autophagy and apoptotic Caspase-3/Caspase-9, and downregulated Nrf2-ARE pathway in the hippocampus CA1 region. Systemic administration of UTI attenuated autophagy and apoptosis, and largely restored Nrf2-ARE signal pathway following cerebral ischemia and thereby alleviated neurological deficits with increasing survival of CA rats. Our data suggest that UTI improves the worsened protein expression of autophagy and apoptosis, and restores Nrf2-ARE signals in the hippocampus and this is linked to inhibition of neurological deficiencies in transient cerebral ischemia. UTI plays a beneficial role in modulating neurological deficits induced by transient cerebral ischemia via central autophagy, apoptosis and Nrf2-ARE mechanisms.