Down regulation of U2AF1 promotes ARV7 splicing and prostate cancer progression.

The present study aims to investigate the roles of U2 Small Nuclear RNA Auxiliary Factor 1 (U2AF1) in the resistance to anti-androgen treatment in prostate cancer and its underlying mechanism. U2AF1 and androgen receptor variant 7 (ARV7) knockdown and overexpression were introduced in PC3 and DU145 cells. In addition, a bicalutamide-resistant PC3 (PC3 BR) cell line was also constructed. Cell count, MTT and soft agar colony formation assays were performed to evaluate cell proliferation. qRT-PCR was applied to determine the mRNA levels of U2AF1, ARV7 and Mitogen-Activated Protein Kinase 1 (MAPK1). Western blot was used to determine the MAPK1 protein expression. A negative correlation between ARV7 and U2AF1 in prostate tumor tissues was observed. U2AF1 downregulation was correlated with poor prognosis in prostate cancer patients. U2AF1 exhibited a negative correlation with ARV7 and its downregulation promoted prostate cancer cell proliferation and bicalutamide resistance. The regulatory effects of U2AF1 on ARV7 splicing were associated with MAPK1. U2AF1 affected prostate cancer proliferation and anti-androgen resistance by regulating ARV7 splicing.

The RNA-binding protein FXR1 modulates prostate cancer progression by regulating FBXO4.

This paper is to characterize the expression status of Fragile X Mental Retardation, Autosomal Homolog 1 (FXR1) in prostate cancer cells and understand its mechanistic involvement in the tumor biology of prostate cancer. The relative expression of FXR1 in prostate cancer cells was determined by real-time polymerase chain reaction and Western blotting. Cell proliferation in FXR1-deficient cells was evaluated by cell counting and MTT assays. The migrative and invasive capacities were measured by transwell assay. The potential regulatory effect of FXR1 on FBXO4 was interrogated using luciferase reporter assay. The direct bind of FXR1 with FBXO4 transcripts was analyzed by RNA immunoprecipitation and RNA pull-down assay. We observed aberrant overexpression of FXR1 in prostate cancer cells at both transcript and protein levels. FXR1 deficiency was associated with inhibited cell proliferation/viability and compromised migration/invasion in prostate cancer cells. Mechanistically, FXR1 negatively regulated FBXO4 transcripts via direct association with its 3'UTR and promoted mRNA degradation. FBXO4 knockdown predominantly rescued the tumor-suppressive phenotype in FXR1-deficient cells. We uncovered the oncogenic role of FXR1 in prostate cancer cells and further demonstrated its dependence on FBXO4. Our data highlight the importance of FXR1-FBXO4 signaling in prostate cancer.

MiR-199a suppresses prostate cancer paclitaxel resistance by targeting YES1.

PURPOSE: Prostate cancer chemoresistance is a major contributor to the poor survival of patients. MicroRNAs (miRNAs) play an important role in regulating cancer resistance. Here we aim to explore the role and mechanism of miR-199a in regulating prostate cancer resistance. METHODS: MiR-199a expressions in human prostate cancer tissues and cell lines were investigated with real-time PCR (RT-PCR). MiR-199a was ectopically overexpressed in PC3 cells, and resistance to paclitaxel (PTX) was evaluated consequently. The interaction between miR-199a and the oncogene Yamaguchi sarcoma viral homolog 1 (YES1) was assessed after miR-199a overexpression. YES1 was ectopically overexpressed, followed by evaluation of PTX resistance. The efficacy of miR-199a as a therapeutic agent was also investigated in vivo. RESULTS: Downregulation of miR-199a was characteristic of prostate cancer, particularly recurrent cancers. MiR-199a was suppressed in PTX-resistant cell line. Overexpression of miR-199a inhibited PTX resistance. YES1 was a target of miR-199a, and overexpression of YES1 reversed the effect of miR-199a in suppressing PTX resistance. In vivo, miR-199a increased tumor PTX sensitivity. CONCLUSIONS: The downregulation of miR-199a contributes to PTX resistance in prostate cancer. YES1 mediates the regulation of miR-199a in prostate cancer PTX resistance. This miR-199a replacement therapy has potential to overcome PTX resistance.

Zhoushi Qi Ling decoction inhibits the progression of castration-resistant prostate cancer in vivo by regulating macrophage infiltration via IL6-STAT3 signaling.

Background and aim: Prostate cancer is a leading malignant tumor in men, associated with a high rate of mortality. Androgen deprivation therapy is commonly used to treat prostate cancer, which contributes to the progression of castration-resistant prostate cancer (CRPC). The current therapy has a low survival rate in patients with CRPC. Our study aims to develop a novel effective approach for CRPC treatment and improve survival benefits. Experimental procedure: CRPC cell line PC-3-Luc expressing luciferase and the CRPC cell line PC-3-IL6-Luc stably overexpressing IL-6 were used to establish the xenograft tumor mouse model. The tumor was monitored weekly using Bioluminescence imaging. Infiltrated macrophages were quantified by fluorescence-activated cell sorting using flow cytometry. IL6 mRNA level was determined using quantitative real-time PCR. The protein levels of total STAT3 and phosphorylated STAT3 were determined using Western blot. Results and conclusion: Zhoushi Qi Ling decoction (ZQD) treatment significantly reduced PC3 the xenograft tumor progression and the number of infiltrated macrophages when compared with saline treatment. IL6 mRNA level was remarkedly suppressed by ZQD treatment. Notably, the protein level of phosphorylated STAT3 was significantly decreased in PC3 the xenograft tumor treated with ZQD compared to saline treatment. Our findings demonstrated that ZQD treatment significantly reduced the progression of prostate cancer, evidenced by the reduced population of infiltrated macrophages and the inhibition of the IL6/STAT3 pathway.

[Clinical efficacy of Shuganyiyang capsule combined with Western medicine for the treatment of type III prostatitis complicated by erectile dysfunction].

OBJECTIVE: To investigate the clinical efficacy of Shuganyiyang Capsule combined with conventional Western medicine (tamsulosin hydrochloride sustained release tablets + prostat tablets) for the treatment of type III prostatitis complicated by erectile dysfunction (ED). METHODS: Eighty patients with type III prostatitis complicated by ED were equally randomized to an experimental and a control group, the former treated with Shuganyiyang Capsule combined with tamsulosin hydrochloride sustained release tablets and prostat tablets, while the latter with tamsulosin hydrochloride and prostat only, both for 8 weeks. Then the prostatitis symptoms, erectile function and psychological conditions of the patients were evaluated using NIH-CPSI, IIEF-5, and hospital anxiety and depression scale (HADA and HADD) respectively. The rates of recovery, excellence, effectiveness and ineffectiveness were calculated. RESULTS: The scores on NIH-CPSI, IIEF-5, HADA and HADD obtained at 4 and 8 weeks after treatment showed statistically significant differences between the two time points as well as from the baseline (P < 0.01). At 8 weeks, the scores on NIH-CPSI, IIEF-5, HADA and HADD were 6.83 +/- 4.96, 21.03 +/- 2.54, 6.05 +/- 1.62, and 5.35 +/- 3.30 in the experimental group, as compared with 7.55 +/- 4.89, 17.68 +/- 4.15, 6.88 +/- 2.45, and 7.85 +/- 3.77 in the control (P < 0.05). The rate of effectiveness was significantly higher in the experimental than in the control group (90% [36/40] vs 70% [28/40], P < 0.05). CONCLUSION: Shuganyiyang Capsule combined with conventional Western medicine, such as alpha blockers and galenica, produces definite effect on chronic prostatitis complicated by ED, improves the psychological conditions of the patient, and enhances the therapeutic efficiency of chronic prostatits.

QiLing Decoction promotes ferroptosis of castration-resistant prostate cancer cells by inhibiting FSP1 in vitro and in vivo.

QiLing Decoction (QLD) showed therapeutic effects against prostate cancer with an unclear underlying mechanism. This study explored the underlying mechanisms of QLD against castration-resistant prostate cancer (CRPC). Clinical specimens were collected from the patients with CRPC. Stable cells including knockdown and overexpression cell lines were established by plasmid transfection. The xenograft animal model was constructed. Cell viability was determined by using cell-counting kit 8 assay. Biochemical assays were used to determine the levels of iron (Fe2+) and lipid reactive oxygen species (ROS). qRT-PCR and Western blotting were used to determine levels of target genes, respectively. Treatment of QLD inhibited ferroptosis suppressor protein (FSP) 1 at mRNA and protein levels in patients with CRPC. Additionally, cells treated with QLD-containing serum displayed a decrease in cell viability and an increase in Fe2+ and lipid ROS with or without erastin, whereas ferroptosis inhibitor reversed QLD-induced ferroptosis. The regulatory effects of QLD on PC3 cell ferroptosis were associated with its inhibitory effects against FSP1. Consistently, QLD inhibited PC3 tumor growth by inhibiting FSP1. Moreover, treatment of QLD increased the sensitivity of PC3-AbiR cells to abiraterone by inhibiting FSP1. QLD promoted ferroptosis in CRPC cells in part by inhibiting FSP1 in vitro and in vivo.

Zhoushi Qiling decoction inhibits proliferation of human prostate cancer cells through IL6/STAT3 pathway.

Background: Prostate cancer is the most common malignant tumor in men, accounting for one of the top five cancer incidences worldwide. However, there is no effective pharmacological treatment for advanced prostate cancer (APC). Herein, we aim to investigate the mechanism of Zhoushi Qiling decoction (ZQD), a traditional Chinese medicine compound, in inhibiting prostate cancer cells proliferation and tumor growth. Methods: IC50 was determined in PC3 and DU145 cells. Cell viability was determined using MTT assay after interleukin (IL) 6 stimulation. Cell proliferation ability was evaluated using colony formation assay. IL-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway was analyzed using qRT-PCR and Western blot in PC3 and DU145 cells and xenograft tumor tissues. Results: It was found that ZQD significantly inhibited Il-6-induced cell viability and proliferation in PC3 and DU145 cells. Moreover, ZQD significantly reduced mRNA levels of IL-6, IL-1ß, STAT3, Bcl2, and CyclinD1, stimulated by IL-6. The protein levels of p-STAT3, Bcl2 and CyclinD1 were reduced by ZQD treatment at 40 mg/mL both in PC3 and DU145 cells. Additionally, in xenograft tumor tissues, tumor volume, weight and proliferation were significantly reduced by ZQD treatment. In addition, the mRNA and protein levels of IL-6 and pSTAT3 were significantly inhibited by ZQD treatment in vivo. Conclusion: We demonstrate that ZQD can effectively reduce cell proliferation and tumor growth by inhibiting the activation of IL-6/STAT3 signaling pathway.

STL127705 synergize with olaparib in castration-resistant prostate cancer by inhibiting homologous recombination and non-homologous end-joining repair.

Therapeutic resistance to androgen-deprivation therapy is a major challenge for prostate cancer therapy. The present study aims to explore the effects of poly (ADP-ribose) polymerase (PARP) inhibitor olaparib and STL127705 on castration-resistant prostate cancer. Cell lines including PC-3 and enzalutamide-resistant LNCaP (erLNCaP) cells were treated with enzalutamide, enzalutamide plus olaparib, enzalutamide plus STL127705, or the combination of olaparib, STL127705, and enzalutamide. Cell viabilities and cell apoptosis were determined using the sulforhodamine B (SRB) assay and Annexin V/propidium iodide staining, respectively. Flow cytometry assay was applied to determine γH2AX intensity and the percentage of homologous recombination and non-homologous end-joining. Besides, a tumor-bearing animal model was established and treated with drugs as for cell lines. STL127705 and olaparib enhanced cytotoxicity of enzalutamide on erLNCaP and PC-3 cells. Furthermore, STL127705 and olaparib promoted enzalutamide-induced cell apoptosis and enhanced γH2AX intensity. In vitro study also showed that the combination of STL127705, olaparib, and enzalutamide inhibited homologous recombination and non-homologous end-joining repair systems in PC-3 cells. In vivo study demonstrated that the combination of STL127705, olaparib, and enzalutamide exhibited a significant anti-tumor effect. STL127705 combined with olaparib have a potential therapeutic effect on castration-resistant prostate cancer through inhibiting homologous recombination and non-homologous end-joining repair.

JNK promotes the progression of castration-resistant prostate cancer.

BACKGROUND: Prostate cancer is one of the most common cancers in men worldwide. This study aims to elucidate the roles of c-Jun N-terminal kinase (JNK) in the progression of castration-resistant prostate cancer (CRPC). METHODS: JNK overexpressing and knockdown cell lines were established on the PC-3 prostate cell line. qPCR and Western blotting were performed to determine the mRNA and protein levels of target genes in prostate tissues and cell lines. MTT and Matrigel invasion assays were conducted to evaluate the cell viability and invasive ability, respectively. The Kaplan-Meier estimator was performed to estimate the overall survival rate and second progression-free survival rate. Pearson's correlation coefficient was used to evaluate the relationship between JNK and prostate-specific antigen (PSA). RESULTS: Relative JNK expression was correlated with Gleason score and PSA value in patients with CRPC. Kaplan-Meier analysis revealed that patients with low JNK expression exhibited high overall survival and second progression-free survival rate. In vitro assays demonstrated that JNK overexpression promoted cell viability and invasion as well as the protein expressions of extracellular signal-regulated kinase (ERK) and matrix metalloproteinase 1 (MMP1) in PC-3 cell lines. CONCLUSIONS: JNK overexpression promotes the development of CRPC via the regulation of ERK and MMP1.

Qi Ling decreases paclitaxel resistance in the human prostate cancer by reversing tumor-associated macrophages function.

Tumor-associated macrophages (TAMs) are critical immune cells infiltrated into tumor. In present study, we evaluated the effects of Qi Ling (QL), a traditional Chinese medicine on paclitaxel resistance in prostate cancer cells and explored the underlying mechanisms. We administrated QL to rats and collected the serum from QL-treated rats (QL-serum). We established the co-culture system of TAMs/paclitaxel resistant prostate cancer cells. We treated the TAMs with QL-serum and measured the viability of paclitaxel resistant prostate cancer cells after exposing to paclitaxel. We monitored the expression of M1 and M2 markers, the expression and activation of IL-6/STAT3 signaling pathways in TAMs after QL treatment. We treated TAMs with QL-serum together with interleukin (IL)-6, measured the expression of M1 and M2 markers, and the viability of paclitaxel resistant prostate cancer cells. In co-culture system, QL-serum-treated TAMs decreased the paclitaxel resistance in the human prostate cancer cells. QL-serum treatment significantly up-regulated the expression of M1 markers inducible nitric oxide synthase and tumor necrosis factor α while decreased the expression of M2 markers IL-10 and chemokine (C-C motif) ligand 22. QL-serum suppressed the activation of IL-6/ signal transducer and activator of transcription 3 signaling pathway. All these effects of QL-serum were abolished in the presence of IL-6. Qi Ling re-programmed TAMs and decreases paclitaxel resistance in prostate cancer cells.

Therapeutic targets and signaling pathways of active components of QiLing decoction against castration-resistant prostate cancer based on network pharmacology.

QiLing decoction (QLD) is a traditional Chinese medicine compound. This study aims to explore the therapeutic effect of QLD in castration-resistant prostate cancer (CRPC) and its potential bio-targets. A total of 51 active components and QLD 149 targets were identified using bioinformatics analysis. Additionally, five optimal hub target genes were screened including tumor protein P53 (TP53), interleukin-6 (IL-6), vascular endothelial growth factor-A (VEGF-A), caspase-3 (CASP-3), and estrogen receptor-1 (ESR-1). The interrelated network between active components of QLD and their potential targets was constructed. The molecular function, biological processes, and signaling pathways of QLD-against CRPC were identified. Moreover, QLD was found to efficiently exert a repressive effect on CRPC tumor growth mainly by suppressing the activation of HIF-α/VEGFA and TNF-α/IL6 signaling pathways, and increasing the P53 expression level. These results successfully indicated the potential anti-CRPC mechanism of the active components of QLD.

miR-143 mediates abiraterone acetate resistance by regulating the JNK/Bcl-2 signaling pathway in prostate cancer.

Background: miR-143 is known to be downregulated in various cancer cells and tumors and generally plays a tumor-suppressor role. miR-143. However, the role of miR-143 in the mediation of the sensitivity of prostate cancer cells to abiraterone acetate remains unrevealed. Methods: The expression levels of miRNAs were determined by miRNA microarray and quantitative real-time PCR (qRT-PCR). The protein levels were assessed by Western blot assay. Cell viability and apoptosis were respectively measured by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Results: We identified that miR-143 was significantly downregulated in PC3-AbiR cells compared to PC3 cells. Overexpression of miR-143 promoted PC-AbiR sensitivity to abiraterone acetate in vitro and in vivo. We also revealed that miR-143 upregulation inhibited p-JNK (c-Jun N-terminal kinases) and increased p-Bcl2 (B-cell lymphoma 2), contributing to abiraterone acetate-induced apoptosis in PC3-AbiR cells. Finally, we showed that the combination of miR-143 and abiraterone acetate exerted the most profound tumor inhibition effect and prolonged the mice survival rate in PC3-AbiR tumor-bearing mice. Conclusion: Upregulation of miR-143 may serve as a new strategy to enhance the therapeutical effect of abiraterone acetate on prostate cancer patients who are resistant to abiraterone acetate.

Qi Ling decoction enhances abiraterone treatment via suppression of autophagy in castration resistant prostate cancer.

Abiraterone acetate has exhibited impressive results in improving progression-free survival of patients with metastatic castration-resistant prostate cancer. However, many patients may develop abiraterone resistance with a variable duration of response. Hence, identifying a remedy to overcome abiraterone resistance is critical for patients with castration-resistant prostate cancer. In this study, we aim to explore the potential of Qi Ling decoction (QLD), a traditional Chinese medicine, in attenuating abiraterone resistance in prostate cancer. Cell viability and apoptosis were respectively measured by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The protein levels were assessed by Western blotting assay. Autophagosome formation was quantified by counting LC3 puncta. We found that QLD was capable of promoting abiraterone-induced apoptosis and cell death of PC3-AbiR and DU145-AbiR cells in vitro. A combination of QLD and abiraterone yielded a better tumor inhibition effect than QLD alone and abiraterone alone. Further investigation revealed that QLD restored the abiraterone sensitivity of PC3-AbiR and DU145-AbiR cells through modulating autophagy. These findings suggest that QLD might serve as a potential remedy to enhance the therapeutical effect of abiraterone for patients with castration-resistant prostate cancer.

Qi Ling Inhibits Progression of Androgen-Independent Prostate Cancer via Negative Regulation of TRIM66/HP1γ/AR Axis.

AIM: This study aimed to understand the molecular mechanism underlying the therapeutic effect of Qi Ling (QL) against androgen-independent prostate cancer. METHODS: The relative expression of TRIM66 in prostate tumor was interrogated by microarray. Real-time polymerase chain reaction and Western blotting were performed to determine the transcript abundances and protein expressions of TRIM66, HP1γ, AR, c-Myc, and GAPDH. Cell proliferation and apoptosis were analyzed by cell counting kit-8 method and flow cytometry. The regulatory action of c-Myc on TRIM66 was interrogated with luciferase reporter plasmid and the direct binding was demonstrated by chromatin immunoprecipitation. The secretory prostate-specific antigen was quantified by enzyme-linked immunosorbent assay. RESULTS: TRIM66 was aberrantly overexpressed in prostate cancer and associated with unfavorable prognosis. TRIM66/HP1γ/AR was upregulated during the androgen-independent transition in hormone-deprived medium. The TRIM66 level positively linked to cell proliferation and negatively linked to cell apoptosis in androgen-independent prostate cancer cells. QL treatment specifically inhibited c-Myc and therefore directly downregulated TRIM66 via binding to its promoter. Ectopic introduction of TRIM66 significantly reversed the anti-tumor effects of QL against androgen-independent prostate cancer. CONCLUSION: Our study uncovered the importance of downregulated TRIM66/HP1γ/AR signaling in mediating the anti-tumor properties of QL.

Effects of Xialiqi capsules on rats with nonbacterial prostatitis.

OBJECTIVE: To investigate the feasibility and effectiveness of Xialiqi capsules in rats with nonbacterial prostatitis. METHODS: A total of 90 healthy male SD rats, weighing 200-220 g, were randomly divided into a blank control group (BCG, n=30), a model group (MG, n=30), and an intervention group (IG, n=30). After establishing the model of chronic nonbacterial prostatitis, IG was treated with 50 mg/kg Xialiqi capsules via gavage. The three groups received the same dose of saline via gavage for 7 consecutive days. The differences in leukocytes, phospholipid vesicle density, number of colonies, prostate mass, apparent diffusion coefficient (ADC), degree of inflammatory cell infiltration in the prostate fluid, serum tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, CD3+, CD8+ levels after intervention were compared in the three groups. RESULTS: Compared with the BCG, the number of leukocytes and colonies in the prostate fluid of the MG was elevated, and the density of lipid vesicles was decreased, and the number of leukocytes and colonies in the prostate fluid of the MG significantly decreased and the density of lipid vesicles rebounded after the intervention of Xialiqi capsules (P>0.05). Compared with the BCG, the prostate mass, ADC and the degree of inflammatory cell infiltration were elevated in the MG. There was a significant reversion of the above indices after the intervention of Xialiqi capsules (P<0.05). The serum levels of TNF-α, IL-6 and IL-8 in the MG were significantly higher than those in the IG, and the levels in the IG were higher than that in the BCG (P<0.05). The serum levels of CD3+ and CD8+ in the MG were significantly lower than those in the IG, and the levels in the IG were lower than that in the BCG (P<0.05). CONCLUSION: Xialiqi capsules have a good intervention effect on nonbacterial prostatitis, which can significantly alleviate the immune status and reduce the level of cytokines in the serum and tissues of rats.

Zhoushi Qiling decoction induces apoptosis of human prostate cancer cells via miR-143/Bcl-2 axis.

A number of traditional Chinese medicines (TCMs) are widely used in prostate cancer treatment in China. The aim of this study was to test the efficacy of a TCM, Zhoushi Qiling Decoction (ZQD), in combination with androgen deprivation therapy (ADT) and explore its underlying mechanism. A total of 151 patients were recruited to receive ADT treatment or ADT+ZQD treatment. The survival of patients who received ADT+ZQD treatment was significantly higher than those who received ADT therapy only. DU145 prostate cancer cells were treated with ZQD (50 mg/mL) for 24 h in vitro and expression levels of an array of miRNAs were examined. Our results suggested that miR-143 demonstrated prominent upregulation in DU145 cells after treatment with ZQD. In patient serum samples, miR-143 expression was also significantly upregulated after ADT+ZQE treatment, which was however absent in patients treated with ADT only. In DU145 cells, ZQD treatment led to a dose-dependent increase in apoptosis, which could be reduced by anti-miR-143 treatment. There was a binding site between miR-143 and B cell CLL/lymphoma-2 (Bcl-2) and ZQD treatment reduced Bcl-2 expression. ZQD treatment led to increased caspase-3 and Bax expression. ZQD treatment could promote apoptosis of prostate cancer cells by promoting miR-143 upregulation, which could be a possible mechanism underlying the inhibitory effect of ZQD in prostate cancer in patient.

RNA-seq reveals microRNA-302b as a suppressor of prostate cancer epithelial-mesenchymal transition by targeting RELA/NF-κB.

To identify novel biomarker(s) in prostate cancer and demonstrate the mechanistic involvements in this disease, RNA-seq was employed to reveal the differentially expressed genes in the blood samples from prostate cancer patients. Relative expression of miR-302b-3p was evaluated using real-time PCR. The potential regulation of RELA by miR-302b-3p was assessed by luciferase reporter assay. Protein levels of NF-κB, Vimentin, N-cadherin and E-cadherin, were quantified using western blotting. Transwell chamber was employed to measure cell migratory and invasive capacity, while cell attachment/detachment assay was performed to evaluated epithelial-mesenchymal transition (EMT)-related behavior. Xenograft tumor model was adopted to determine the anti-tumor activity of miR-302b-3p in vivo. We demonstrated miR-302b-3p was down-regulated in prostate cancer both in vivo and in vitro. We predicted and identified RELA as directly targeted by miR-302b-3p. Ectopic miR-302b-3p expression in PC-3 cells significantly suppressed cell migration, invasion, attachment, detachment capacity, which was accompanied with a decrease in the expression of N-cadherin and Vimentin, and an increase of E-cadherin expression. MiR-302b-3p-proficiency greatly delayed xenograft tumor growth and associated with favorable overall survival. Co-introduction of RELA completely abolished anti-tumor effects of miR-302b-3p, which indicated a potential genetic interaction between RELA/NF-κB and miR-302b-3p. We characterized the aberrant down-regulation of miR-302b-3p in prostate cancer and unraveled a possible involvement of miR-302b-3p/RELA signaling axis in this scenario.

Zhoushi Qi Ling decoction represses docetaxel resistance and glycolysis of castration-resistant prostate cancer via regulation of SNHG10/miR-1271-5p/TRIM66 axis.

Docetaxel resistance developed in half of castration-resistant prostate cancer (CRPC) patients hinders its long-term clinical application. The current study was designed to investigate the effects of Chinese medicine Zhoushi Qi Ling decoction on the docetaxel resistance of prostate cancer as well as elucidate the underlying molecular mechanism. In our study, Qi Ling significantly decreased viability and colony formation as well as increased apoptosis of docetaxel-resistant (DR) CRPC cells. Qi Ling-treated DR cells exhibited decreased glucose consumption, lactate release and pyruvate production. Moreover, lncRNA SNHG10 was upregulated in DR tissues of CRPC patients and was negatively correlated with the progression-free survival. Bioinformatics analysis indicated miR-1271-5p as the associated miRNA possibly binding with SNHG10. miR-1271-5p up-regulation dramatically decreased the luciferase activity of SNHG10 in DR cells. SNHG10 knockdown sharply increased the expression of miR1271-5p in DR cells. Targetscan predicted TRIM66 as one of the downstream targets of miR-1271-5p. miR-1271-5p up-regulation drastically reduced luciferase activity as well as TRIM66 expression in DR cells. Also, the knockdown of SNHG10 remarkably suppressed the expression of TRIM66 in DR cells. Additionally, Qi Ling treatment reduced SNHG10 and TRIM66, while increased miR1271-5p, in DR cells. In summary, Qi Ling inhibited docetaxel resistance and glycolysis of CRPC possibly via SNHG10/miR-1271-5p/TRIM66 pathway.

TRIM66 promotes malignant progression of prostate carcinoma through the JAK/STAT pathway.

Prostate cancer is the fifth leading cause of cancer-related deaths in males globally. Tripartite Motif Containing 66 (TRIM66) functions as transcriptional repressor and exerts its effect at least partially through promotion of deacetylase. TRIM66 has been previously reported to play an oncogenic role in a number of human cancers. Here, we investigated the potential oncogenic properties of TRIM66 in prostate cancer. We report that shRNA-mediated knockdown of TRIM66 significantly suppressed viability and proliferation of both PC-3 and DU145 prostate cancer cell lines. Furthermore, TRIM66 deficiency inhibited migration and invasion of prostate cancer cells. Mechanistically, TRIM66 positively regulated signal transducer and activator of transcription 2 (STAT2) and interleukin-2 (IL-2) expression. The predominance of STAT2-IL-2 in mediating the oncogenic properties of TRIM66 was determined using a rescue assay, wherein overexpression of either STAT2 or IL-2 almost completely abolished the inhibitory effects on cell proliferation, migration and invasion elicited by TRIM66 deficiency in prostate cancer cells. Our study highlights the importance of the TRIM66-STAT2-IL-2 signaling axis in the tumor biology of prostate cancer.

Lobaplatin Inhibits Prostate Cancer Proliferation and Migration Through Regulation of BCL2 and BAX.

Lobaplatin is a diastereometric mixture of platinum (II) complexes, which contain a 1,2-bis (aminomethyl) cyclobutane stable ligand and lactic acid. Previous studies have showed that lobaplatin plays inhibiting roles in various types of tumors. However, the role of lobaplatin in prostate cancer remains unknown. Cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cell proliferation was detected by cell colony formation assay. Cell migration and invasion were determined by transwell migration and invasion assay. Cell apoptosis was detected by flow cytometry. The messenger RNA and protein expression levels were detected by quantitative real-time polymerase chain reaction and Western blot. Lobaplatin treatment inhibits cell viability, cell proliferation, cell migration, and invasion, while promotes cell apoptosis of prostate cancer cell lines DU145 and PC3. Meanwhile, lobaplatin treatment regulates apoptosis by downregulation of BCL2 expression and upregulation of BAX expression levels. Our study suggests lobaplatin inhibits prostate cancer proliferation and migration through regulation of BCL2 and BAX expression.