Pro-oncogene FBI-1 inhibits the ferroptosis of prostate carcinoma PC-3 cells via the microRNA-324-3p/GPX4 axis.

Ferroptosis has been characterized as non-apoptotic programmed cell death and is considered a novel strategy for antitumor treatment. The factor that binds to inducer of short transcripts-1 (FBI-1) is an important proto-oncogene playing multiple roles in human malignancies and the development of resistance to therapy. However, the roles of FBI-1 in ferroptosis of endocrine independent prostate carcinoma are still unknown. The results of this study showed that FBI-1 inhibited the ferroptosis of prostate carcinoma PC-3 cells (a typical endocrine-independent prostate carcinoma cell line) via the miR-324-3p/glutathione peroxidase 4 (miR-324-3p/GPX4) axis. Overexpression of FBI-1 enhanced the expression levels of GPX4. In contrast, knockdown of FBI-1 decreased the expression of GPX4 and induced the ferroptosis of PC-3 cells. The miR-324-3p decreased the expression of GPX4 by targeting the 3'-untranslated region of GPX4 to induce ferroptosis. Notably, FBI-1 increased the expression of GPX4 by repressing the levels of miR-324-3p. The transcription of miR-324-3p was mediated by specificity protein 1 (SP1), and FBI-1 repressed the expression of miR-324-3p by repressing the activation of SP1. In clinical specimens, the endogenous levels of FBI-1 were positively associated with Glutathione Peroxidase 4 (GPX4) and negatively related with the expression of miR-324-3p. Therefore, the results indicated that the miR-324-3p/GPX4 axis participates in the FBI-1-mediated ferroptosis of prostate carcinoma cells.

The functional implication of ATF6α in castration-resistant prostate cancer cells.

Stress in the endoplasmic reticulum (ER) may perturb proteostasis and activates the unfolded protein response (UPR). UPR activation is frequently observed in cancer cells and is believed to fuel cancer progression. Here, we report that one of the three UPR sensors, ATF6α, was associated with prostate cancer (PCa) development, while both genetic and pharmacological inhibition of ATF6α impaired the survival of castration-resistance PCa (CRPC) cells. Transcriptomic analyses identified the molecular pathways deregulated upon ATF6α depletion, and also discovered considerable disparity in global gene expression between ATF6α knockdown and Ceapin-A7 treatment. In addition, combined analyses of human CRPC bulk RNA-seq and single-cell RNA-seq (scRNA-seq) public datasets confirmed that CRPC tumors with higher ATF6α activity displayed higher androgen receptor (AR) activity, proliferative and neuroendocrine (NE) like phenotypes, as well as immunosuppressive features. Lastly, we identified a 14-gene set as ATF6α NE gene signature with encouraging prognostic power. In conclusion, our results indicate that ATF6α is correlated with PCa progression and is functionally relevant to CRPC cell survival. Both specificity and efficacy of ATF6α inhibitors require further refinement and evaluation.

IDO promotes the proliferation and invasion of prostate cancer cells through KYNU.

BACKGROUND: Prostate cancer (PCa) is one of the most common malignant tumors in male. OBJECTIVE: To explore the effect of indoleamine-2, 3-dioxygenase (IDO) on the proliferation and invasion of PCa cells and the potential mechanism. METHODS: PCa tissues and normal adjacent tissues were collected from 43 PCa patients. The expression of IDO in PCa tissues and cell lines were detected. The String website was used to search for IDO-related proteins. The GEPIA website was used to analyze the relationship between KYNU and the prognosis of PCa. Cells models of IDO overexpression and/or KYNU silencing were constructed to verify the role of KYNU in regulating PCa. The cell proliferation, apoptosis and invasion ability of PCa cells were detected by CCK-8 assay, Flow cytometry and Transwell assay. RESULTS: The IDO levels in PCa tissues and cells were higher than those in normal tissues and cells, which promoted the proliferation and invasion of LNCaP cells, and inhibited apoptosis. Silencing IDO inhibited the cells proliferation and invasion activities, and promoted the cell apoptosis. The high expression of KYNU was related to the poor disease free survival of PCa patients. Inhibiting KYUN significantly inhibited the promotion of PCa induced by IDO. CONCLUSION: IDO is overexpressed in PCa, which promotes the proliferation and invasion of PCa cells, and the cancer-promoting mechanism may be related to KYNU.

High-performance scanning-mode polarization based computational ghost imaging (SPCGI).

Computational ghost imaging (CGI) uses preset patterns and single-pixel detection, breaking through the traditional form of point-to-point imaging. In this paper, based on the Monte Carlo model, a reflective polarization based CGI (PCGI) system has been proposed and constructed under the foggy environments. And the imaging performances of the PCGI at different optical distances have been investigated and analyzed quantitatively. When the targets and the background have a small difference in reflectivity, the difference of polarization characteristics between the targets and the background can help the CGI to remove the interference of scattering light and improve the imaging contrast. Besides, in order to further improve imaging efficiency, a scanning-mode polarization based CGI (SPCGI) has also been proposed, in which the combination of polarization characteristics and the scanning-mode plays an important role to improve the CGI's imaging efficiency and imaging quality.

Measuring glucose concentration in a solution based on the indices of polarimetric purity.

Polarization imaging is a powerful tool, which can be applied in biomedical diagnosis and many research fields. Here, we propose a new application of the indices of polarimetric purity (IPPs) composed of P1, P2, P3, to describe the glucose concentrations (GC) changes in the scattering system. The results suggest that P1 of the IPPs is a better indicator to GC in the solution than the degree of polarization (DoP) for the forward scattering detection. Meanwhile, the fitting relation among radius of scattering particle, GCs and P1 parameter has also been calculated, in which the error of inversion is no more than 4.73%. In the backscattering detection, the fitted frequency statistical histogram of the IPPs is used to measure the GCs, and their modes can represent changing trend of GCs.

Clinical significance of EPHX2 deregulation in prostate cancer.

The arachidonic acid (AA) metabolic pathway participates in various physiological processes as well as in the development of malignancies. We analyzed genomic alterations in AA metabolic enzymes in the Cancer Genome Atlas (TCGA) prostate cancer (PCa) dataset and found that the gene encoding soluble epoxide hydrolase (EPHX2) is frequently deleted in PCa. EPHX2 mRNA and protein expression in PCa was examined in multiple datasets by differential gene expression analysis and in a tissue microarray by immunohistochemistry. The expression data were analyzed in conjunction with clinicopathological variables. Both the mRNA and protein expression levels of EPHX2 were significantly decreased in tumors compared with normal prostate tissues and were inversely correlated with the Gleason grade and disease-free survival time. Furthermore, EPHX2 mRNA expression was significantly decreased in metastatic and recurrent PCa compared with localized and primary PCa, respectively. In addition, EPHX2 protein expression correlated negatively with Ki67 expression. In conclusion, EPHX2 deregulation is significantly correlated with the clinical characteristics of PCa progression and may serve as a prognostic marker for PCa.

Long Non-coding RNA AGAP2-AS1 Silencing Inhibits PDLIM5 Expression Impeding Prostate Cancer Progression via Up-Regulation of MicroRNA-195-5p.

Prostate cancer remains a significant cause of cancer-related deaths in male population. More recently, accumulating evidence continues to implicate long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in various types of cancers, including prostate cancer. The current study aimed to elucidate the role of lncRNA AGAP2-AS1/miR-195-5p/PDZ and LIM domain 5 (PDLIM5) in prostate cancer progression. Initially, microarray expression profiles were applied to screen differentially expressed lncRNAs/miRNAs/genes associated with prostate cancer. Dual-luciferase reporter and RNA pull-down/RIP assays were subsequently performed to explore the interactions among lncRNA AGAP2-AS1, miR-195-5p, and PDLIM5, after which their expression was detected in cancer tissues and cells. Next, gain- and loss-of-function approaches were employed to elucidate the mechanism of lncRNA AGAP2-AS1/miR-195-5p/PDLIM5 in the processes of cell proliferation, migration and invasion as well as tumor growth. LncRNA AGAP2-AS1 was found to be highly expressed in prostate cancer. Silencing of lncRNA AGAP2-AS1 contributed to the suppression of proliferation, migration and invasion of cancer cells in vitro. Besides, lncRNA AGAP2-AS1 could bind to miR-195-5p which targeted PDLIM5 and subsequently downregulated its expression, ultimately impeding the progression of prostate cancer. Additionally, lncRNA AGAP2-AS1 inhibition led to an up-regulated expression of miR-195-5p and down-regulated PDLIM5 expression, resulting in delayed tumor growth in vivo. Taken together, the key findings of our study demonstrated that lncRNA AGAP2-AS1 silencing exerted suppressive effects on the development of prostate cancer via the miR-195-5p-dependent downregulation of PDLIM5. Our findings highlighted the potential of lncRNA AGAP2-AS1 as a promising novel molecular target for prostate cancer therapy.

[Expressions of phospho-Erk1/2 and phospho-Akt1 in the corpus cavernosum of aged rats].

OBJECTIVE: Nitric oxide (NO) is a key factor for penile erection. Its generation is mainly regulated by nitric oxide synthase (NOS), while both phospho-Erkl/2 (P-Erkl/2) and phospho-Aktl (P-Aktl) can affect the expression and activity of NOS and consequently penile erection. This experiment aimed to study the expressions of P-Erkl/2 and P-Aktl in the corpus cavernosum and their possible roles in erectile dysfunction in aged rats. METHODS: We included 10 two-month-old male SD rats in Group A and another 10 eighteen-month-old ones in Group B, measured the levels of serum testosterone, and detected the expressions of P-Erkl/2 and P-Aktl in the corpus cavernosum by immunohistochemistry and RT-PCR. RESULTS: Compared with Group A, Group B showed a significantly decreased level of serum testosterone (9.57 +/- 1.57 nmol/L vs 4.73 +/- 0.94 nmol/L, P < 0.05), and remarkably increased mRNA expressions of P-Erk1 and P-Erk2 and protein expression of P-Erkl/2 (0.47 +/- 0.09, 0.61 +/- 0.11 and 7.50 +/- 1.81 vs 0.95 +/- 0.06, 0.92 +/- 0.05 and 32.09 +/- 8.45, P < 0.05). But there were no significant differences in the mRNA and protein expressions of P-Akt1 between the two groups (0.97 +/- 0.04 and 11.67 +/- 5.61 vs 0.94 +/- 0.05 and 10.93 +/- 3.06, P > 0.05). CONCLUSION: The overexpression of P-Erk1/2 in the corpus cavernous may be one of the important mechanisms of aging-related erectile dysfunction.

[Raf/MEK/ERK1/2 signaling pathway and penile erection].

Penile erection is regulated by the relaxation of corpus cavernosum smooth muscle cells (CCSMCs). It has been recognized that the Ras/MEK/ERK1/2 signaling pathway is closely related to the functions of CCSMCs and endothelial cells, and it is involved in the regulation of penile erection, mainly via phosphorylation of NO synthase. ERK1/2 phosphorylates, inhibits eNOS activity, and thus reduces the relaxation of CCSMCs and penile erection. But the site of phosphorylation is not yet clear. In CCSMCs and endothelial cells, the ERK1/2 pathway interacts with other cascades and regulates the erectile function of the penis. This article presents an overview of the researches on the ERK1/2 signaling cascade, its regulatory role and its interaction with other signaling pathways in penile erection.

[Expressions of Erk1/2 and PKB/Akt in the corpus cavernosum of castrated rats].

OBJECTIVE: To study the expressions of Erk1/2 and PKB/Akt in the corpus cavernosum of castrated rats and investigate their action mechanism in the development of erectile dysfunction (ED) after castration. METHODS: We randomly divided 20 eight-week-old SD rats into Groups A (sham-operation) and B (castration), and, 4 weeks after the operation, determined the level of serum testosterone (T) and the expressions of P-Erk1/2 and P-PKB/Akt proteins (integrated optical density/area, IA/area) and those of Erk1/2 and PKB/Akt mRNA (Marker: GAPDH) in the corpus cavernosum of the rats by immunohistochemical staining and RT-PCR. RESULTS: Four weeks after the operation, the serum T level was significantly decreased in Group B in comparison with A ([10.090 +/- 3. 026] nmol/L versus [1.339 +/- 0.642] nmol/L, P < 0.05). Erk1/2 and PKB/Akt expressed in the corpus cavernosum of both groups of rats. The expressions of Erk1 and Erk2 mRNA and P-Erk1/2 were significantly higher in Group B (0. 840 +/- 0.062, 0.876 +/- 0.141 and 0.142 +/- 0.020) than in A (0.479 +/- 0.090, 0.599 +/- 0.100 and 0.119 +/- 0.029) (P < 0.05). But no statistically significant differences were found in the expressions of PKB/Akt mRNA and P-PKB/Akt between Groups B (0.974 +/- 0.040 and 0.164 +/- 0.036) and A (0.942 +/- 0.054 and 0.162 +/- 0.025) (P < 0.05). CONCLUSION: Erk1/2 and PKB/Akt expressed in the penile tissues of both castrated and sham-operation rats. The increased expression of P-Erk1/2 in the corpus cavernosum may be involved in the development of ED in castrated rats.

[Expressions of phospho-Erk1/2 and phospho-Akt1 in the corpus cavernosum of spontaneous hypertensive rats].

OBJECTIVE: To understand the expressions of phosphor Erk1/2 (P-Erk1/2) and phosphor Akt1 (P-Akt1) in the corpus cavernosum of spontaneous hypertensive (SH) and normotensive rats, and to investigate their relationship with penile erectile function. METHODS: A series of electric stimuli were applied to the corpus cavernosum nerves of 8 SH rats, the changes of ICP/MAP observed continuously, and the expressions of P-Erk1/2 and P-Akt1 in the corpus cavernosum detected by immunohistochemistry and RT-PCR. Another 8 male WKY rats were taken as controls. RESULTS: ICP/MAP was significantly lower in the SH rats than in the controls (P < 0.01). The mRNA expressions of P-Erk1 and P-Erk2 and the protein expression of P-Erk1/2 were significantly increased in the SH group (0.81 +/- 0.05, 0.91 +/- 0.06 and 54.22 +/- 10.05), as compared with 0.42 +/- 0.04, 0.68 +/- 0.14 and 7.05 +/- 1.45 in the WKY rats (P < 0.05). The mRNA and protein levels of P-Akt exhibited no significant differences between the SH and control groups (0.90 +/- 0.05 and 11.17 +/- 2.21 versus 0.92 +/- 0.06 and 10.91 +/- 1.86, P > 0.05). CONCLUSION: Erectile dysfunction in hypertension patients is associated with the overexpression of P-Erk1/2 in the cavernous tissue, but not obviously correlated with the expression of P-Akt1.