Tissue damage from chronic liver injury inhibits peripheral NK cell abundance and proinflammatory function.

One of the difficulties in the treatment of hepatocellular carcinoma is that it is impossible to eliminate the inhibitory effect of the tumor microenvironment on immune response. Therefore, it is particularly important to understand the formation process of the tumor microenvironment. Chronic inflammation is the core factor of cancer occurrence and the leading stage of inflammation-cancer transformation, and the natural killer cell subsets play an important role in it. Our study confirmed that in the stage of chronic liver injury, the local immunosuppressive microenvironment of the liver (i.e. the damaged microenvironment) has been formed, but this inhibitory effect is only for peripheral natural killer cells and has no effect on tissue-resident natural killer subsets. The markers of damage microenvironment are the same as those of tumor microenvironment.

YY1 complex in M2 macrophage promotes prostate cancer progression by upregulating IL-6.

BACKGROUND: Tumor-associated macrophages are mainly polarized into the M2 phenotype, remodeling the tumor microenvironment and promoting tumor progression by secreting various cytokines. METHODS: Tissue microarray consisting of prostate cancer (PCa), normal prostate, and lymph node metastatic samples from patients with PCa were stained with Yin Yang 1 (YY1) and CD163. Transgenic mice overexpressing YY1 were constructed to observe PCa tumorigenesis. Furthermore, in vivo and in vitro experiments, including CRISPR-Cas9 knock-out, RNA sequencing, chromatin immunoprecipitation (ChIP) sequencing, and liquid-liquid phase separation (LLPS) assays, were performed to investigate the role and mechanism of YY1 in M2 macrophages and PCa tumor microenvironment. RESULTS: YY1 was highly expressed in M2 macrophages in PCa and was associated with poorer clinical outcomes. The proportion of tumor-infiltrated M2 macrophages increased in transgenic mice overexpressing YY1. In contrast, the proliferation and activity of anti-tumoral T lymphocytes were suppressed. Treatment targeting YY1 on M2 macrophages using an M2-targeting peptide-modified liposome carrier suppressed PCa cell lung metastasis and generated synergistic anti-tumoral effects with PD-1 blockade. IL-4/STAT6 pathway regulated YY1, and YY1 increased the macrophage-induced PCa progression by upregulating IL-6. Furthermore, by conducting H3K27ac-ChIP-seq in M2 macrophages and THP-1, we found that thousands of enhancers were gained during M2 macrophage polarization, and these M2-specific enhancers were enriched in YY1 ChIP-seq signals. In addition, an M2-specific IL-6 enhancer upregulated IL-6 expression through long-range chromatin interaction with IL-6 promoter in M2 macrophages. During M2 macrophage polarization, YY1 formed an LLPS, in which p300, p65, and CEBPB acted as transcriptional cofactors. CONCLUSIONS: Phase separation of the YY1 complex in M2 macrophages upregulated IL-6 by promoting IL-6 enhancer-promoter interactions, thereby increasing PCa progression.

Immune activation is essential for the antitumor activity of EZH2 inhibition in urothelial carcinoma.

The long-term survival of patients with advanced urothelial carcinoma (UCa) is limited because of innate resistance to treatment. We identified elevated expression of the histone methyltransferase EZH2 as a hallmark of aggressive UCa and hypothesized that EZH2 inhibition, via a small-molecule catalytic inhibitor, might have antitumor effects in UCa. Here, in a carcinogen-induced mouse bladder cancer model, a reduction in tumor progression and an increase in immune infiltration upon EZH2 inhibition were observed. Treatment of mice with EZH2i causes an increase in MHC class II expression in the urothelium and can activate infiltrating T cells. Unexpectedly, we found that the lack of an intact adaptive immune system completely abolishes the antitumor effects induced by EZH2 catalytic inhibition. These findings show that immune evasion is the only important determinant for the efficacy of EZH2 catalytic inhibition treatment in a UCa model.

The role of γδ T17 cells in cardiovascular disease.

Due to the ability of γδ T cells to bridge adaptive and innate immunity, γδ T cells can respond to a variety of molecular cues and acquire the ability to induce a variety of cytokines such as IL-17 family, IFN-γ, IL-4, and IL-10. IL-17+ γδ T cells (γδ T17 cells) populations have recently received considerable interest as they are the major early source of IL-17A in many immune response models. However, the exact mechanism of γδ T17 cells is still poorly understood, especially in the context of cardiovascular disease (CVD). CVD is the leading cause of death in the world, and it tends to be younger. Here, we offer a review of the cardiovascular inflammatory and immune functions of γδ T17 cells in order to understand their role in CVD, which may be the key to developing new clinical applications.

Transgenic construction and functional miRNA analysis identify the role of miR-7 in prostate cancer suppression.

Although miR-7 suppresses the initiation and progression in cancers, little is known about its role in prostate cancer, especially in transgenic mouse models. In present study, we found that expression of miR-7, regulated by p53, was lower in prostate cancer tissues, and miR-7 overexpression significantly mitigated prostate cancer cells growth both in vitro, in organoids and in vivo regardless of p53 status. After we generated miR-7 overexpression transgenic mice and miR-7+/TRAMP mice, we found that transgenic overexpression of miR-7 in mice is safe and miR-7+/TRAMP mice have a preferred overall survival. Moreover, in vivo treatment of miR-7 inhibited subcutaneous tumour growth in mice and prolonged the survival of mice harboring prostate cancer lung metastasis when co-injection with PD-1 antibody. In addition, miR-7 downregulated glycolysis of prostate cancer cells by inhibiting several key pathways including HIF-1α, and subsequently remodeled acidic tumour microenvironment, PanKLa level and T cell infiltration. In summary, our findings highlighted a promising target for development of miRNA-based therapeutics for prostate cancer patients regardless of p53 status.

Associations between exposure to different heavy metals and self-reported erectile dysfunction: a population-based study using data from the 2001-2004 National Health and Nutrition Examination Survey.

Heavy metals are ubiquitous and nonbiodegradable pollutants that are widely distributed in the environment. Heavy metal exposure can damage various biological tissues and cause several diseases. This study aimed to investigate the association between blood and urinary cadmium, lead, and mercury levels and erectile dysfunction (ED) based on data from the 2001-2004 National Health and Nutrition Examination Survey. In total, 3681 participants were included in the analysis. Results showed that participants with ED had high blood cadmium, mercury, creatinine, urinary lead, cadmium levels, low blood lead, serum cotinine, and urinary mercury levels. Multivariate logistic regression analysis showed that only blood cadmium level was an independent risk factor of ED (tertile [T]2 vs T1: odds ratio = 1.495, 95% confidence interval: 1.181-1.892, p = 0.001; T3 vs T1: odds ratio = 2.089, 95% confidence interval: 1.554-2.809, p < 0.001). The dose-response curve showed a positive nonlinear association between blood cadmium and lead levels and ED and a negative nonlinear association between blood and urinary mercury levels and ED after propensity score matching. In conclusion, heavy metal exposure is closely correlated with the development of ED, and a high blood cadmium level is an independent risk factor of ED.

Association of Long Non-Coding RNA MEG3 Polymorphisms and Risk of Prostate Cancer in Chinese Han Population.

PURPOSE: To explore the association between MEG3 polymorphisms and the risk of prostate cancer in the Chinese Han population. MATERIALS AND METHODS: Two MEG3 single-nucleotide polymorphisms (SNPs) (rs11627993 C >T rs7158663 A>G) were genotyped in a case-control study in which 165 prostate cancer patients and 200 healthy controls were recruited by a Real-Time Polymerase Chain Reaction (PCR) with the TaqMan assay. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of association. RESULTS: No statistically significant differences were found in the allele or genotype distributions of the MEG3 rs11627993 C >T and rs7158663 A > G polymorphisms among cases or healthy control subjects (rs11627993: CC vs CA: 95% CI = 0.54-1.95, ORs = 1.03; CC vs AA: 95% CI = 0.67-2.54, ORs = 1.30 ; CC/CA vs AA: 95% CI = 0.81-1.98, ORs = 1.26 , P = .29 ; C vs A: 95% CI = 0.85-1.57, ORs = 1.16, P = .35; rs7158663: AA vs AG: 95% CI = 0.76-5.08, ORs = 1.97, AA vs GG: 95% CI = 0.57-3.29, ORs = 1.37; AA/AG vs GG : 95% CI = 0.56-1.32, ORs = 0.86, P = .49; A vs G: 95% CI = 0.69-1.39, ORs = 0.98, P = .91) Further stratified analysis detected no significant association. CONCLUSION: The MEG3 polymorphisms (rs11627993 C>T and rs7158663 A>G) does not influence the susceptibility to prostate cancer.

miR-143 inhibits renal cell carcinoma cells metastatic potential by suppressing ABL2.

Although micro RNA (miRNA) expression profiles are widely investigated in renal cell carcinoma (RCC), their potential roles for affecting RCC initiation and progression remain largely unknown. Here, we examined the aberrant expression profiles of miRNAs inhuman metastatic RCC tissues based on Gene Expression Omnibus (GSE37989). We further validated them iRNAs expression data in the largest clinical dataset: The Cancer Genome Atlas (TCGA). And cell adhesion and migration abilities and epithelial me senchymal transition (EMT) related proteins were assessed in both normal and tumor RCC cell lines. We suggest that hsa-miR-143 is a potential tumor suppressor in RCC as its down regulation positively correlated with adverse prognosis. Biologically, cell adhesion, migration, and EMT were dramatically inhibited by miR-143. Mechanistically, we found that miR-143 targets ABL proto-oncogene 2 (ABL2), which was also found to be an indicator for poor survival in TCGA database. Our results have important implications in understanding functions of miRNAs in metastatic RCC and will provide a basis for further clinical application.

Association between lncRNA H19 polymorphisms and cancer susceptibility based on a meta-analysis from 25 studies.

BACKGROUND: Long non-coding RNA H19 polymorphisms were reported to be related to cancer susceptibility. However, the results from individual studies have been controversial or inconsistent. To clarify the associations between H19 single nucleotide polymorphisms (rs2107425, rs217727, rs2735971, rs2839698, rs3024270, and rs3741219) and the cancer susceptibility more accurately. METHODS: Relevant publications were searched from PubMed and EMBASE up to May 31, 2019, for studies in English only. The reference lists of the retrieved studies were also investigated. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to find out the relationship between the H19 polymorphisms and cancer susceptibility. All of the data were analyzed using Stata 12.0. RESULTS: The results showed that rs2107425 polymorphisms was associated with an increasing cancer susceptibility in Asian (T vs C: OR 1.13, 95% CI 1.01-1.28; TT + CT vs CC: OR 1.21, 95% CI 1.03-1.44; CT vs CC: OR 1.21, 95% CI 1.01-1.44) and decreasing risk in Caucasian (T vs C: OR 0.90, 95% CI 0.84-0.97; TT + CT vs CC: OR 0.84, 95% CI 0.75-0.94; CT vs CC: OR 0.82, 95% CI 0.72-0.94). And rs217727 polymorphism was associated with an increasing cancer susceptibility in the Asian (A vs G: OR 1.09, 95% CI 1.02-1.17; AA + GA vs GG: OR 1.12, 95% CI 1.01-1.21; AA vs GG: OR 1.18, 95% CI 1.02-1.36). Additionally, rs2839698 polymorphism was associated with an increasing risk overall (A vs G: OR 1.18, 95% CI 1.06-1.31), in breast cancer (A vs G: OR 1.67, 95% CI 1.14-2.45; AA + AG vs GG: OR 1.98, 95% CI 1.20-3.25; AG vs GG: OR 1.89, 95% CI 1.16-3.07), in Asian (A vs G: OR 1.09, 95% CI 1.03-1.14; AA + AG vs GG: OR 1.11, 95% CI 1.04-1.21; AA vs AG + GG: OR 1.12, 95% CI 1.01-1.25; AA vs GG: OR 1.15, 95% CI 1.01-1.49; AG vs GG: OR 1.09, 95% CI 1.02-1.17), and in Caucasian (AA vs AG + GG: OR 1.81, 95% CI 1.25-2.61). CONCLUSION: H19 rs2107425, rs217727 and rs2839698 were associated with an increasing cancer susceptibility in Asian. Rs2107425 was associated with a decreasing risk and rs2839698 was associated with an increasing risk in Caucasian. No significant association was found in H19 rs2735971, rs3024270 and rs3741219 polymorphisms and cancer susceptibility.

Association of Hsa-miR-23a rs3745453 variation with prostate cancer risk among Chinese Han population: A case-control study.

Prostate cancer (PCa) is a frequently diagnosed malignant solid tumor in men. The etiology of PCa has been attributed to both environmental and genetic factors. In recent years, many studies have reported that miRNA gene single-nucleotide polymorphisms (SNPs) influence the susceptibility to several diseases such as cancer. To date, the mechanisms of PCa have remained unknown. The main aim of this study was to evaluate the association between PCa susceptibility and miRNA gene SNPs. A total of 156 PCa cases and 188 control subjects were included in this case-control study. The data were collected from hospitalized cases. We collected the demographic characteristic information, which included age, body mass index, tobacco smoking, alcohol consumption, and family history of cancer. Polymorphisms were analyzed by the ligase detection reaction. Unconditional logistic and stratified analyses were used to analyze the association between these SNPs and PCa susceptibility and to calculate the adjusted odds ratios (ORs) and the 95% confidence intervals (CIs). Cox regression model and the log-rank test were used to test the association between genetic variants and the overall survival. We found that miR-23a gene polymorphism rs3745453 carrying CC homozygotes had a 4.16-fold increased risk (95% CI = 1.30-13.25) than those carrying the TT/CT genotypes (P = .02), and the C allele displayed a higher prevalence of PCa than the T allele (OR = 1.68, 95% CI = 1.16-2.45, P = .01). Moreover, miR-23a showed that the homozygous carriers of the C-variant significantly increased the risk of survival rate as compared to the carriers of the TT/CT genotype (OR = 9.67, 95% CI = 2.83-33.09, P = .001). The rs3745453 polymorphism was potentially associated with PCa in the Chinese Han population and had an interactive relationship with the environmental factors.

LncRNA CCAT1 Promotes Prostate Cancer Cell Proliferation by Interacting with DDX5 and MIR-28-5P.

Accumulated evidence indicates that CCAT1 functions as an oncogene in the progression of a variety of tumors. However, little is known as to how CCAT1 impacts tumorigenesis in human prostate cancer. In this study, we found from The Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center database that CCAT1 is highly upregulated in castration-resistant prostate cancer (CRPC) compared with androgen-dependent prostate cancer (ADPC). Higher level of CCAT1 leads to increased mortality in patients with CRPC. In vitro and in vivo studies show that CCAT1 promotes prostate cancer cell proliferation as well as the tumor growth of prostate cancer xenografts. Mechanistically, in cytoplasm, CCAT1 sponges MIR-28-5P to prevent the anticancer effect. In nucleus, CCAT1 acts as a scaffold for DDX5 (P68) and AR transcriptional complex to facilitate the expression of AR-regulated genes, thus stimulating CRPC progression. Our findings suggest that CCAT1 is an oncogenic factor in the progression of CRPC with different regulatory mechanisms in the nucleus and cytoplasm of cells.

MicroRNA-200a suppresses prostate cancer progression through BRD4/AR signaling pathway.

Prostate cancer is still considered a significant health care challenge worldwide due in part to the distinct transformation of androgen-dependent prostate cancer (ADPC) into treatment-refractory castration-resistant prostate cancer (CRPC). Consequently, there is an urgent need to explore novel molecular mechanisms underlying treatment resistance in ADPC. Although numerous studies have alluded to the role of miR-200a in several cancers, the biological significance of miR-200a in prostate cancer remains unknown. After performing microarray analysis and reanalysis of the publicly available Memorial Sloan Kettering Cancer Center dataset, miR-200a expression was found higher in ADPC tissues and its expression was positively associated with survival of CRPC patients. In vitro studies showed that miR-200a overexpression in CRPC cells markedly suppressed cellular proliferation and facilitated apoptosis. In vivo studies indicated that overexpression of miR-200a inhibited growth and metastasis of prostate cancer. The luciferase reporter assay demonstrated that BRD4 is a direct target gene of miR-200a and it could reverse miR-200a-mediated biological effects in prostate cancer cells. Most importantly, our findings indicated that miR-200a suppresses the progression of CRPC by inhibiting the activation of BRD4-mediated AR signaling. This finding provides the foundation for the development of more personalized therapeutic approaches for CRPC patients.

[Establishment of enzalutamide-resistant human prostate cancer cell lines and screening of lncRNA and mRNA expression profiles].

OBJECTIVE: To establish enzalutamide-resistant human prostate cancer cell lines and screen out the lncRNA and mRNA expression profiles associated with enzalutamide resistance. METHODS: Human prostate cancer cell lines LNCAP and C4-2B were cultured with 10 µmol/L enzalutamide for 6 months in vitro for the establishment of enzalutamide-resistant subclones LNCAP-ENZA and C4-2B-ENZA. The IC50 value and enzalutamide resistance index of each cell line were examined by MTT assay, the expressions of enzalutamide-related genes FL-AR, AR-V7 and HnRNPA1 were determined by Western blot, and the lncRNA and mRNA differential expressions of C4-2B and C4-2B-ENZA were detected by high-throughout lncRNA microarray. RESULTS: Compared with LNCAP and C4-2B, the IC50 values of enzalutamide-resistant subclones LNCAP-ENZA (60.83 µmol/L) and C4-2B-ENZA (88.32 µmol/L) were increased significantly (P < 0.05) and the enzalutamide-resistance indexes of the LNCAP-ENZA and C4-2B-ENZA cells were 4.94 and 4.67, respectively. The expressions of AR-V7 and HnRNPA1 were markedly up-regulated in the LNCAP-ENZA and C4-2B-ENZA cells as compared with those in the LNCAP and C4-2B cells, but that of FL-AR showed no significant change. A total of 1 440 lncRNAs and 1 236 mRNAs were identified as differentially expressed in the C4-2B-ENZA cells. CONCLUSIONS: Enzalutamide -resistant human prostate cancer cell subclones LNCAP-ENZA and C4-2B-ENZA were successfully established and enzalutamide resistance-associated lncRNA and mRNA were identified, which may provide some molecular evidence for the management of enzalutamide-resistant human prostate cancer.

Aloperine executes antitumor effects through the induction of apoptosis and cell cycle arrest in prostate cancer in vitro and in vivo.

BACKGROUND: Prostate cancer (PCa) is one of the most common malignant diseases among male patients. Although androgen deprivation therapy remains the main treatment for PCa, most patients would inevitably progress to castration-resistant PCa, which is the main cause of cancer-related deaths. Thus, novel antitumor agents are urgently needed. Recent studies demonstrated that aloperine (ALO) as a natural alkaloid showed antitumor effects in other cancer types. However, the biological function and underlying mechanisms of ALO in PCa have not been investigated. METHODS: PCa cell lines including LNCaP, PC3 and DU145 were cultured and treated with ALO. Cell Counting Kit-8 assay, colony formation assay, apoptosis assay and cell cycle assay were conducted to assess the biological role of ALO. In addition, a PCa subcutaneous xenograft mouse model was established to evaluate the role of ALO in terms of proliferation and apoptosis in vivo. We further measured the protein expression levels of p-Akt/Akt, p-ERK/ERK, c-Myc, cleaved caspase 3, p21, p53, Bcl-2 and Bax using the Western blot 48 h after ALO treatment of PCa cells. RESULTS: ALO effectively inhibited the cell viability of PCa by inducing cell cycle arrest via the activation of the p53/p21 pathway and triggering apoptosis in vitro and in vivo. ALO also inhibited phosphorylation of Akt and ERK protein kinases and activated cleaved caspase 3 while exerting antiproliferation function through inducing apoptosis and cell cycle arrest in PCa cells. CONCLUSION: Based on our findings, we conclude that ALO could suppress the tumor growth and promote cell apoptosis and cell cycle arrest in PCa cells, which indicated that ALO could act as a novel therapeutic agent in treatment of human PCa.

Effects of four single nucleotide polymorphisms of EZH2 on cancer risk: a systematic review and meta-analysis.

BACKGROUND: Although the relationship between several single nucleotide polymorphisms (SNPs) of the oncogene EZH2 and cancer risk has been assessed by some case-control studies, results of subsequent studies are controversial. Sample sizes from single-center studies are also limited, thereby providing unreliable findings. Hence, we conducted a comprehensive search and meta-analysis to evaluate the associations between EZH2 SNPs and cancer risk. MATERIALS AND METHODS: A comprehensive literature search for studies focusing on EZH2 SNPs and cancer risk was conducted on PubMed, Web of Science, Embase, and China National Knowledge Infrastructure online databases. Genotype data were extracted and examined through a meta-analysis, and pooled odds ratios (ORs) with 95% CIs were used to assess the corresponding associations. Sensitivity analysis, publication bias assessment, and heterogeneity test were performed using STATA 12.0. RESULTS: Twelve eligible studies were included in this meta-analysis. The association of 4 SNPs, namely, rs887569, rs2302427, rs3757441, and rs41277434, in the EZH2 locus with cancer risk was evaluated. Five studies (1,794 cases and 1,878 controls) indicated that rs887569 was related to a decreased cancer risk (CTTT/CC: OR =0.849, 95% CI: [0.740 to 0.973], P=0.019; TT/CCCT: OR =0.793, 95% CI: [0.654 to 0.962], P=0.019). Seven studies (2,408 cases and 2,910 controls) showed that rs2302427 was linked to a decreased cancer risk (GG/CC: OR =0.562, 95% CI: [0.400 to 0.792], P=0.001; CGGG/CC: OR =0.856, 95% CI: [0.748 to 0.980], P=0.024; GG/CCCG: OR =0.733, 95% CI: [0.571 to 0.940], P=0.015). No relationships were observed between rs3757441 or rs41277434 and cancer risk. CONCLUSION: rs887569 and rs2302427 in EZH2 may be correlated with a decreased cancer risk. Although rs3757441 and rs41277434 are independent risk factors of cancer, further large-scale and functional studies are warranted to validate our findings.

Involvement of aberrantly activated HOTAIR/EZH2/miR-193a feedback loop in progression of prostate cancer.

BACKGROUND: Though androgen deprivation therapy is the standard treatment for prostate cancer (PCa), most patients would inevitably progress to castration-resistant prostate cancer (CRPC) which is the main cause of PCa death. Therefore, the identification of novel molecular mechanism regulating cancer progression and achievement of new insight into target therapy would be necessary for improving the benefits of PCa patients. This study aims to study the function and regulatory mechanism of HOTAIR/EZH2/miR-193a feedback loop in PCa progression. METHODS: MSKCC and TCGA datasets were used to identify miR-193a expression profile in PCa. Cell Counting Kit-8 (CCK-8) assays, colony formation, invasion, migration, flow cytometry, a xenograft model and Gene Set Enrichment Analysis were used to detect and analyze the biological function of miR-193a. Then, we assessed the role of HOTAIR and EZH2 in regulation of miR-193a expression by using plasmid, lentivirus and small interfering RNA (siRNA). Luciferase reporter assays and chromatin immunoprecipitation assays were performed to detect the transcriptional activation of miR-193a by EZH2 and HOTAIR. Further, qRT-PCR and luciferase reporter assays were conducted to examine the regulatory role of miR-193a controlling the HOTAIR expression in PCa. Finally, the correlation between HOTAIR, EZH2 and miR-193a expression were analyzed using In situ hybridization and immunohistochemistry. RESULTS: We found that miR-193a was significantly downregulated in metastatic PCa through mining MSKCC and TCGA datasets. In vitro studies revealed that miR-193a inhibited PCa cell growth, suppressed migration and invasion, and promoted apoptosis; in vivo results demonstrated that overexpression of miR-193a mediated by lentivirus dramatically reduced PCa xenograft tumor growth. Importantly, we found EZH2 coupled with HOTAIR to repress miR-193a expression through trimethylation of H3K27 at miR-193a promoter in PC3 and DU145 cells. Interestingly, further evidence illustrated that miR-193a directly targets HOTAIR showing as significantly reduced HOTAIR level in miR-193a overexpressed cells and tissues. The expression level of miR-193a was inversely associated with that of HOTAIR and EZH2 in PCa. CONCLUSION: This study firstly demonstrated that miR-193a acted as tumor suppressor in CRPC and the autoregulatory feedback loop of HOTAIR/EZH2/miR-193a served an important mechanism in PCa development. Targeting this aberrantly activated feedback loop may provide a potential therapeutic strategy.

MicroRNA-744 promotes prostate cancer progression through aberrantly activating Wnt/ß-catenin signaling.

Accumulated evidence indicate that miR-744 functions as either tumor suppressor or oncogene in the progression of a variety of tumors, with a tumor type-specific way. However, little is known about how miR-744 impacts on the tumorigenesis of human prostate cancer. In this study, employing the analyses of microarray, qRT-PCR and re-analysis of MSKCC data, we found that CRPC tissues expressed much more miR-744 than ADPC tissues did, and the expression level of miR-744 was inversely associated with survival of CRPC patients. In vitro studies revealed that miR-744 promotes PCa cells proliferation, enhances migration, invasion; in vivo results demonstrated that silencing of miR-744 mediated by shRNA dramatically reduces PCa xenograft tumor growth. Importantly, through human gene expression array, pathway enrichment analysis and Western blot, we identified that miR-744 dramatically activated Wnt/ß-catenin pathway by targeting multiple negative regulators of Wnt/ß-catenin signaling, including SFRP1, GSK3ß, TLE3 and NKD1. At molecular level, we further defined that NKD1 is a major functional target of miR-744. Our findings indicate that miR-744 acts as one of oncogenic factor in the progression of CRPC by recruiting a mechanism of aberrant activation of Wnt/ß-catenin signaling.