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.

Background: Dibutyl phthalate (DBP) was an endocrine disruptor, which may lead to cancer and affects reproductive function when accumulated in the body. But the precise role of DBP in the reproductive system remained controversial.Objective: We employed the meta-analysis to explore the relationship between DBP and reproductive-related outcomes.Methods: We searched relevant literature in PubMed, EMBASE, and Web of Science databases. The standardized mean differences (SMDs) and their 95% CIs were measured by random-effects models. Funnel plots and Egger’s regression test were applied to assess publication bias.Results: Finally, 19 literatures were included in this research. The outcomes revealed that DBP was negatively correlated with reproductive organs weight (testis weight: SMD: −0.59; 95% Cl: −1.23, −0.23; seminal vesicles weight: SMD: −0.74; 95% Cl: −1.21, −0.27; prostate weight: SMD: −0.46; 95% Cl: −0.76, −0.16) and sperm parameters (sperm morphology: SMD: 1.29; 95% Cl: 0.63, 1.94; sperm count: SMD: −1.81; 95% Cl: −2.39, −1.23; sperm motility: SMD: −1.92; 95% Cl: −2.62, −1.23).Conclusion: Our research demonstrated that DBP may be negatively associated with reproductive-related indicators, especially at Gestation exposure period and middle dose (100–500 mg/kg/day).

Abstract. Peptidyl-prolylcis-trans isomerase NIMAinteracting 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.

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.

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Background Extensive research has revealed that tumor stemness plays a central role in promoting tumor progression. However, the underlying involvement of stemness-related genes in renal clear cell carcinoma (ccRCC) remains controversial. Methods The data used for bioinformatics analysis were downloaded from The Cancer Genome Atlas database. The R software, SPSS and GraphPad Prism 8 were used for mapping and statistical analysis. Results We first quantified the stemness index of each patient through a machine learning algorithm. Then, we identified the differentially expressed genes between high and low stemness index as stemness-related genes. Based on these genes, we finally established a stable and effective prognosis model to predict patients' overall survival using a random forest algorithm (Training cohort; 1-year AUC: 0.67; 3-year AUC: 0.79; 5-year AUC: 0.73; Validation cohort; 1-year AUC: 0.66; 3-year AUC: 0.71; 5-year AUC: 0.7). The model genes include AC010973.2, RNU6-125P, AP001209.2, Z98885.1, KDM5C-IT1 and AL021368.3. The gene AC010973.2 was selected for further research for its highest importance. In vitro experiments demonstrated that AC010973.2 is highly expressed in ccRCC tissue and cell lines. Meanwhile, knockdown of AC010973.2 could significantly hamper the proliferation of ccRCC cells according to the colony formation and CCK8 assays. Conclusion In summary, our finding indicated that the stemness-related gene AC01097.3 is closely associated with patients' survival and could remarkably facilitate cell proliferation in ccRCC, making it potential to be a novel therapeutic target.

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.

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