Circular RNA circANKS1B acts as a sponge for miR-152-3p and promotes prostate cancer progression by upregulating TGF-α expression.

BACKGROUND: A growing number of studies indicate that circular RNAs (circRNAs) play critical roles in human diseases, and show great potential as biomarkers and therapeutic targets. This study aimed to investigate the expression and function of circANKS1B in prostate cancer (PC). METHODS: The expression of circANKS1B and miR-152-3p was analyzed by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell migration and invasion were measured using a transwell assay. The interaction between circANKS1B and miR-152-3p was confirmed by a dual-luciferase reporter gene assay. Rescue experiments were conducted to determine whether circANKS1B regulated the invasion of PC cells via the circANKS1B-miR-152-3p-TGF-α pathway. RESULTS: The expression of circANKS1B was markedly upregulated in both PC cells and tissues. Moreover, high circANKS1B expression was associated with poor prognosis in PC patients. Dual-luciferase reporter assay indicated that circANKS1B directly bound to miR-152-3p. Furthermore, circANKS1B negatively regulated miR-152-3p expression. Knockdown of circANKS1B markedly suppressed cell migration and invasion and TGF-α expression in PC cells, whereas the effects of circANKS1B silencing were reversed by miR-152-3p deficiency. In addition, the impact of miR-152-3p silencing on invasion of circANKS1B-deficient PC cells was also abrogated by TGF-α deficiency. Overall, circANKS1B acts as a sponge for miR-152-3p to promote PC progression by upregulating TGF-α expression. CONCLUSION: Our findings reveal that circANKS1B may be a potential prognostic biomarker and therapeutic target for PC.

[TURP plus endocrine therapy (ET) versus α1A-blockers plus ET for bladder outlet obstruction in advanced prostate cancer].

OBJECTIVE: To compare the effect of transurethral resection of the prostate combined with endocrine therapy (TURP + ET) with that of αlA-blockers combined with ET ((αlA-b + ET) in the treatment of bladder outlet obstruction (BOO) in patients with advanced prostate cancer (PCa), and to investigate the safety of the TURP + ET for the treatment of PCa with BOO. METHODS: We retrospectively analyzed 63 cases of PCa with BOO, 28 treated by αlA-b + ET and the other 35 by TURP + ET. We obtained the residual urine volume (RV), maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and quality of life score (QoL) before and after treatment along with the overall survival rate of the patients, followed by comparison of the parameters between the two methods. RESULTS: At 3 months after treatment, RV, IPSS, and QoL in the TURP + ET group were significantly decreased from (137.8 ± 27.6) ml, (22.3 ± 3.6), and (4.2 ± 0.8) to (29 ± 13.6) ml, (7.8 ± 2.1), and (1.6 ± 0.5) respectively (P < 0.05), while Qmax increased from (5.6 ± 2.1) ml/s to (17.6 ± 2.7) ml/s (P < 0.05); the former three parameters in the αlA-b + ET group decreased from (133.6 ± 24.9) ml, (21.5 ± 3.2), and (4.7 ± 1.1) to (42 ± 18.3) ml, (12.8 ± 2.6), and (2.5 ± 0.7) respectively (P < 0.05), while the latter one increased from (6.3 ± 2.4) ml/s to (11.7 ± 2.3) ml/s (P < 0.05), all with statistically significant differences between the two groups (P < 0.05). The overall survival rate of the TURP + ET group was not significantly different from that of the αlA-b + ET group (51.4% vs 46.4% , P > 0.05). CONCLUSION: TURP + ET is preferable to αlA-b + ET for its advantage of relieving BOO symptoms in advanced PCa without affecting the overall survival rate of the patients.

miR-152 controls migration and invasive potential by targeting TGFα in prostate cancer cell lines.

BACKGROUND: MicroRNAs (miRNAs) are a class of short non-coding RNAs that function in diverse biological processes. Aberrant miR-152 expression has been frequently reported in various malignant tumors. However, the mechanism of miR-152 in prostate cancer (PCa) remains unclear. This study aims to determine the function of miR-152 in PCa cells and identify the novel molecular targets regulated by miR-152. METHODS: The expression levels of transforming growth factor-alpha (TGFα) were determined in three samples of PCa and adjacent non-tumorous tissues by Western blot analysis. miR-152 levels in 48 primary PCa and 15 non-malignant tissue samples were measured by qRT-PCR. The effects of forced miR-152 expression or TGFα knockdown on PCa cells were evaluated by cell migration and invasion assays, as well as Western blot analysis. Dual-luciferase reporter assay was used to identify binding sites between miR-152 and TGFα 3'-UTR. RESULTS: TGFα was upregulated in PCa tissue samples compared with that in adjacent normal ones. miR-152 expression was significantly decreased in primary PCa samples compared with that in non-malignant samples. Patients with Gleason scores >7 exhibited lower miR-152 levels than those with lower scores. Moreover, low miR-152 expression is correlated with advanced pathological T-stages. Forced miR-152 expression or TGFα knockdown significantly reduced the migratory and invasive capabilities of PCa cells in vitro. TGFα is a direct target gene of miR-152. CONCLUSIONS: Our findings suggest that miR-152 can act as a tumor suppressor that targets TGFα. miR-152 is a promising molecular target that inhibits PCa cell migration and invasion.

miR-154 inhibits EMT by targeting HMGA2 in prostate cancer cells.

Epithelial-mesenchymal transition (EMT) is a crucial process that plays an important role in the invasion and metastasis of human cancers. High-mobility group AT-hook 2 (HMGA2) has been found to be involved in the EMT program, with its aberrant expression having been observed in a variety of malignant tumors. However, the mechanisms regulating HMGA2 expression remain incompletely understood. The objective of this study was to investigate whether mir-154 plays a critical role in EMT by regulating HMGA2. The expression levels of HMGA2 were examined in four samples of prostate cancer (PCa) tissue and adjacent non-tumorous tissue by Western blot analysis. The effects of forced expression of miR-154 or HMGA2 knockdown on PCa cells were evaluated by cell migration and invasion assays and Western blot analysis. HMGA2 was upregulated in the PCa tissue samples compared with the adjacent normal ones. Forced expression of miR-154 or HMGA2 knockdown significantly reduced the migratory and invasive capabilities of PCa cells in vitro and inhibited EMT gene expression, increased the levels of E-cadherin, an epithelial marker, and decreased the levels of vimentin, a mesenchymal marker. HMGA2 is a direct target gene of miR-154 by dual-luciferase reporter assay. Our findings suggest that miR-154 plays a role in regulating EMT by targeting HMGA2. Understanding the targets and regulating pathways of miR-154 may provide new insights into the underlying pathogenesis of PCa.

Identification and validation of DLX4 as a prognostic and diagnostic biomarker for clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a lethal cancer, and biomarkers for exact diagnosis and predicting prognosis are urgently needed. The present study aimed to determine the roles of distal-less homeobox (DLX) family genes in ccRCC. The clinicopathological and mRNA expression data of patients with ccRCC were derived from The Cancer Genome Atlas database. Kaplan-Meier curves, univariate and multivariate Cox hazard analyses, in addition to receiver operator characteristic curves were used to evaluate the prognostic and diagnostic values. A single-sample gene set enrichment analysis was used to quantify the infiltration levels of immune cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were conducted to examine the expression levels of DLX4 in tumor and adjacent tissue; the results demonstrated that DLX4 was highly expressed in ccRCC tissues compared with normal renal tissues. Furthermore, DLX4 expression was associated with tumor stage and grade. High proportions of males, advanced pathological stage, higher tumor grade and T, N and M stage were also observed in the high DLX4 expression group. Patients with the high DLX4 expression levels tended to have lower overall survival and disease-free survival rates compared with those with low DLX4 expression. DLX4 expression also showed favorable diagnostic efficiency in ccRCC patients. Based on functional enrichment analysis, cell cycle related pathways, epithelial-mesenchymal transition, glycolysis and inflammatory response were associated with the expression levels of DLX4. Furthermore, DLX4 expression was revealed to be associated with tumor immunosuppressive microenvironment. Overall, the expression level of DLX4 may be considered a novel prognostic indicator in ccRCC and a specific diagnostic biomarker for patients with ccRCC.

Marital Status and Prognostic Nomogram for Bladder Cancer With Distant Metastasis: A SEER-Based Study.

BACKGROUND: To investigate the impact of marital status on overall survival (OS) and create a prognostic nomogram predicting OS in distant-metastatic bladder cancer (DMBC) patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was explored to recruit DMBC patients from 2010 to 2015. Kaplan-Meier survival analysis was used to compare survival differences among different marital status. Univariate and multivariate analyses were used to screen for prognostic factors and then constructed the nomogram based on Cox proportional hazard regression models. Calibration plot diagrams and concordance index (C-index) were used to verify the prognostic nomogram. RESULTS: Kaplan-Meier curves suggested the significant differences of OS among different marital status existed in total (P < 0.001), female (P = 0.011) and male (P = 0.001) DMBC patients, respectively. Multivariate analysis indicated marital status was an independent prognostic factor for OS of DMBC patients. Nomogram showed the contribution of marital status to predicting OS was small. Other independent prognostic factors included age, grade, histology type, surgery of primary site, chemotherapy, and metastasis pattern. By combining seven factors, we constructed a prognostic nomogram for DMBC patients. The C-index of this nomogram for OS prediction was 0.722 (95% CI 0.712-0.732). The calibration curves showed perfect consistency between observed and predictive survival. CONCLUSIONS: Marital status was an independent prognostic factor for OS of DMBC patients, but its contribution to predicting OS was small. The prognostic nomogram will provide an individualized evaluation of OS and guidance for suitable treatments in DMBC patients.

miR-135b inhibits tumour metastasis in prostate cancer by targeting STAT6.

MicroRNAs (miRNAs) are small non-coding RNAs that participate in several cellular functions and tumour progression. A previous microarray study demonstrated that miR-135b is downregulated in prostate cancer (PCa) cells, but the role and molecular mechanism of miR-135b in the regulation of tumour metastasis remain to be elucidated. In the present study, significant downregulation of miR-135b in PCa tissues, compared with noncancerous tissues, was detected by reverse transcription-quantitative polymerase chain reaction. Furthermore, the expression of miR-135b was demonstrated to be associated with the pathological stage and the levels of total and free prostate-specific antigen (PSA) in PCa cells. In addition, signal transducer and activator of transcription 6 (STAT6) was identified as a target of miR-135b in PCa cells by luciferase activity and western blot assays. The upregulation of miR-135b in PCa cells led to reduced expression of STAT6 in the cytoplasm and nucleus of these cells, while the overexpression of miR-135b and knockdown of STAT6 were able to inhibit the migration and invasion abilities of PCa cells in vitro. Therefore, the results of the present study indicate that miR-135b suppresses tumour metastasis by targeting STAT6.

Lack of association between the PIN1 promoter -667T>C (rs2233679) polymorphism and cancer risk: Evidence from meta-analysis.

Peptidyl-prolylcis-trans isomerase NIMA-interacting 1 (PIN1) is a critical catalyst involved in multiple oncogenic signaling pathways. The PIN1 promoter -667T>C (rs2233679) polymorphism plays a role in cancer risk. The association between PIN1 (-667T>C) polymorphism and cancer risk has been previously investigated. However, the available results are inconclusive. To derive a more precise estimation, a meta-analysis of seven published case-control studies including 4,524 cases with different tumor types and 4,561 controls was performed. Published literature from PubMed and EMBASE was retrieved. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Overall, the results did not suggest any associations between the PIN1 promoter (-667T>C) polymorphism and cancer susceptibility (OR=1.04, 95% CI: 0.91-1.18 for CC vs. TT; OR=0.98, 95% CI: 0.89-1.09 for TC vs. TT; OR=1.00, 95% CI: 0.91-1.10 for TC/CC vs. TT; OR=1.07, 95% CI: 0.97-1.18 for CC vs. TC/TT). Further stratified analysis by cancer type, ethnicity and sample size did not reveal any significant associations in the genetic models. The results of the present study demonstrate that the PIN1 promoter (-667T>C; rs2233679) polymorphism is not associated with cancer susceptibility.

PIN1 promoter polymorphism (-842 G>C) contributes to a decreased risk of cancer: Evidence from meta-analysis.

Peptidyl-prolylcis-trans isomerase NIMA-interacting 1 (encoded by the PIN1 gene) regulates the conformation of proline-directed phosphorylation sites and is important in the etiology of cancer. Since the identification of a functional polymorphism of PIN1, (-842 G>C; rs2233678), in the PIN1 promoter region, numerous studies have evaluated the association between the PIN1 promoter polymorphism (-842 G>C) and cancer risk. However, the available results are inconclusive. To derive a more precise estimation, a meta-analysis of seven previous case-control studies was performed, which included 4,524 cases exhibiting different tumor types and 4,561 control subjects. The published literature was retrieved from PubMed and EMBASE. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Overall, the results of the present study demonstrated that individuals carrying the variant C allele (G/C and C/C) were associated with a significantly decreased cancer risk (OR, 0.75; 95% CI, 0.62-0.90 for GC vs. GG; OR, 0.75; 95% CI, 0.64-0.88 for GC/CC vs. GG). In further stratified analyses, a decreased cancer risk was observed in the following subgroups: Breast and lung cancer patients, Asian individuals, and in studies with a sample size >500. The results indicated that the PIN1 promoter polymorphism (-842 G>C; rs2233678) contributes to a decreased risk of cancer via attenuating the transcriptional activity.

Association of erythropoietin gene rs576236 polymorphism and risk of adrenal tumors in a Chinese population.

Erythropoietin (EPO) is a circulating glycosylated protein hormone and has been implicated in the development and progression of non-hematopoietic tissue tumors. The objective of the present study was to determine if the EPO rs576236 polymorphism was associated with the risk of adrenal tumors. We genotyped the EPO rs576236 polymorphism in a case-control study of 288 adrenal tumor patients and 456 cancer-free controls by using the TaqMan method, and assessed the association between the polymorphism and the adrenal tumor risk by logistic regression. Furthermore, 95% confidence interval (CI) was used to assess the genetic association between the polymorphism and the risk of adrenal tumor. Compared with the TT genotype, the TC genotype had a significantly increased risk of adrenal tumor [adjusted odds ratio (OR)  =  1.24, 95% CI  =  1.12-2.22]. Furthermore a significantly increased risk of adrenal tumor was found in the combined variant genotypes TC+CC compared with the TT genotype (adjusted OR  =  1.17, 95% CI  =  1.12-2.21). Our present study suggests that the rs576236 polymorphism of EPO confers susceptibility to adrenal tumor in the Chinese population.

miR-154 inhibits prostate cancer cell proliferation by targeting CCND2.

BACKGROUND: Research has shown reduced expression levels of miR-154 in prostate cancer (CaP). However, the function and molecular mechanisms of miR-154 in this cancer type remains unknown. OBJECTIVE: The aims of this study were to examine the functional significance of miR-154 in CaP cells and to identify the novel molecular targets regulated by miR-154. MATERIALS AND METHODS: miR-154 expression significantly decreased in primary CaP samples compared with nonmalignant samples measured by quantitative reverse transcription polymerase chain reaction. Restoration of miR-154 lowered the potential of CaP cell lines to grow and proliferate in vitro evaluated by CCK-8 assay, colony formation assay, and flow cytometry. miR-154 down-regulated the expression of CCND2 by binding to its 3'-untranslated region by luciferase reporter assay. CONCLUSIONS: miR-154 plays a prominent role in CaP proliferation by suppressing CCND2, and it may provide a new approach to the treatment of CaP.

Sprouty2 is associated with prognosis and suppresses cell proliferation and invasion in renal cell carcinoma.

OBJECTIVE: To investigate the expression pattern of Sprouty2 (Spry2) and its clinicopathologic significance among patients with renal cell carcinoma (RCC) and to detect its role in proliferation and invasion of RCC in vitro. MATERIALS AND METHODS: The expression profile of Spry2 in RCC and matched adjacent noncancerous tissues were detected by immunohistochemistry and Western blot analysis. The expression of Spry2 was depleted by stably transfecting with small, interfering ribonucleic acid and the effects of Spry2 were assessed using the cell proliferation and transwell assay. RESULTS: We found Spry2 protein expressed at lower levels and modestly downregulated in cancerous RCC tissues compared with adjacent normal tissue (P <.001). We also measured the expression level of Spry2 in 103 archived RCC tissues by immunohistochemical staining and found its correlation with clinicopathologic findings such as tumor size (P = .002), pathologic TNM stage (P <.001), tumor grade (P <.001), lymph node metastasis (P = .001), distant metastasis (P <.001), and poor survival (P = .001). In addition, small interfering ribonucleic acid-induced depletion of Spry2 expression promoted proliferation and invasion in RCC cell lines. CONCLUSION: Collectively, our results have demonstrated for the first time, to our knowledge, that Spry2 might offer an attractive new target for prognostic and therapeutic intervention in RCC.