circSOBP Inhibits Bladder Cancer Proliferation and Metastasis by Regulating the miR-200a-3p/PTEN Axis and Participating in the Immune Response.

A growing body of evidence shows that circular RNAs (circRNAs) participate in tumor growth and metastasis and also play crucial roles in the treatment and prognosis of various cancers. In this article, we identified a novel circRNA, circSOBP (has_circ_0001633), based on the results of high-throughput RNA sequencing, and its expression was subsequently validated via quantitative reverse transcription polymerase chain reaction in bladder cancer (BCa) tissues and cell lines. The association between circSOBP expression and the clinicopathologic features and prognosis of 56 recruited BCa patients was then analyzed, and the biological roles of circSOBP were assessed by in vitro cloning formation, wound healing, transwell, CCK-8, and in vivo xenograft mouse models. Next, the competitive endogenous RNA mechanism was explored through fluorescence in situ hybridization, RNA pull-down, luciferase reporter, bioinformatics analysis, and rescue experiments. Western blot and immunohistochemistry detected the expression of downstream mRNA, and we were able to determine that circSOBP was downregulated in BCa tissues and cell lines and that lower circSOBP expression was associated with more advanced pathological stage, larger tumor size, and poorer overall survival with BCa patients. Overexpressed circSOBP suppressed cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, competitive interactions between circSOBP and miR-200a-3p enhanced target gene PTEN expression. In addition, we found a significant correlation between higher expression of circSOBP in BCa patients after immunotherapy than before and a better treatment outcome, indicating that circSOBP might regulate the programmed death 1/programmed death ligand 1 pathway. Overall, circSOBP inhibits BCa tumorigenesis and metastasis by a novel miR-200a-3p/PTEN axis, which makes it an excellent biomarker and therapeutic target for treating BCa.

CircSTK39 suppresses the proliferation and invasion of bladder cancer by regulating the miR-135a-5p/NR3C2-mediated epithelial-mesenchymal transition signaling pathway.

Circular RNAs (circRNAs) serve as novel noncoding RNAs that have crucial functions in the development of tumors, including those from bladder cancer (BCa). However, the role and underlying molecular mechanism of circRNAs in mediating the epithelial-mesenchymal transition (EMT) processes in BCa have yet to be studied. In this research, we first found a novel circRNA, circSTK39 (termed as has_circ_0001079), which was a downregulated gene based on the results of high-throughput RNA sequencing. Subsequently, we determined that the expression of circSTK39 in BCa tissues and their cell lines was significantly reduced. In addition, lower circSTK39 expression was strongly related to a worse prognosis for BCa patients. Next, we detected the biological functions of circSTK39 by using loss and gain experiments in vitro and in vivo. Ectopic expression of circSTK39 decreased cell proliferation, colony formation, and invasion capacities, while circSTK39 knockdown prevented the above phenotypes. Mechanically, circSTK39 could sponge with miR-135a-5p, thus inhibiting NR3C2-mediated EMT processes in the BCa progression. In conclusion, our results revealed that circSTK39 inhibited EMT of BCa cells through the miR-135a-5p/NR3C2 axis and may provide promising biomarkers for the diagnosis or prospective therapeutic targets for BCa.

Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer.

Increasing evidences have demonstrated that circular RNA (circRNAs) plays a an essential regulatory role in initiation, progression and immunotherapy resistance of various cancers. However, circRNAs have rarely been studied in bladder cancer (BCa). The purpose of this research is to explore new circRNAs and their potential mechanisms in BCa. A novel ceRNA-regulated network, including 87 differentially expressed circRNAs (DE-circRNAs), 126 DE-miRNAs, and 217 DE-mRNAs was constructed to better understanding the biological processes using Cytoscape 3.7.1 based on our previously high-throughput circRNA sequencing and five GEO datasets. Subsequently, five randomly selected circRNAs (upregulated circ_0001681; downregulated circ_0000643, circ_0001798, circ_0006117 and circ_0067900) in 20 pairs of BCa and paracancerous tissues were confirmed using qRT-PCR. Functional analysis results determined that 772 GO functions and 32 KEGG pathways were enriched in the ceRNA network. Ten genes (PFKFB4, EDNRA, GSN, GAS1, PAPPA, DTL, TGFBI, PRSS8, RGS1 and TCF4) were selected for signature construction among the ceRNA network. The Human Protein Atlas (HPA) expression of these genes were consistent with the above sequencing data. Notably, the model was validated in multiple external datasets (GSE13507, GSE31684, GSE48075, IMvigor210 and GSE32894). The immune-infiltration was evaluated by 7 published algorithms (i.e., TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL and EPIC). Next, Correlations between riskscore or risk groups and clinicopathological data, overall survival, recognized immunoregulatory cells or common chemotherapeutic agents of BCa patients were performed using wilcox rank test, chi-square test, cox regression and spearman's correlation analysis; and, these results are significant. According to R package "GSVA" and "clusterProfiler", the most significantly enriched HALLMARK and KEGG pathway was separately the 'Epithelial Mesenchymal Transition' and 'Ecm Receptor Interaction' in the high- vs. low-risk group. Additionally, the functional experiments in vitro also revealed that the overexpression of has_circ_0067900 significantly impaired the proliferation, migration, and invasion capacities of BCa cells. Collectively, the results of the current study provide a novel landscape of circRNA-associated ceRNA-regulated network in BCa. The ceRNA-associated gene model which was constructed presented a high predictive performance for the prognosis, immunotherapeutic responsiveness, and chemotherapeutic sensitivity of BCa. And, has_circ_0067900 was originally proposed as tumor suppressor for patients with BCa.

Upregulated Transcription Factor PITX1 Predicts Poor Prognosis in Kidney Renal Clear Cell Carcinoma-Based Bioinformatic Analysis and Experimental Verification.

Paired-like homeodomain transcription factor 1 (PITX1) is involved in numerous biological processes, including cell growth, progression, and invasion in various malignant tumors. Nevertheless, the relationship between PITX1 and kidney renal clear cell carcinoma (KIRC) remains unclear. The clinical role and functions of PITX1 were analyzed by integrating multiple open-access online datasets. Further experimental verification was performed via quantitative real-time PCR (qRT-PCR) to detect the expression of PITX1 in 10 pairs of KIRC tissues. Our results revealed that PITX1 mRNA was overexpressed in tumor tissues compared with normal tissues in the TCGA-KIRC database (p < 0.001) and numerous independent cohorts (p < 0.05). Further, high expression of PITX1 mRNA was detected in KIRC tissues compared with adjacent normal tissues in our center by qRT-PCR (N = 10, p < 0.05). Logistic regression analysis demonstrated that the PITX1 level was positively associated with KIRC patients, T and M stages, histologic grade, and pathologic stage (all p < 0.05). Survival analysis showed that upregulation of PITX1 mRNA was associated with poor overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) (all p < 0.05). Univariate/multivariate Cox hazard regression analysis revealed that PITX1 was an independent risk factor for OS in patients with KIRC (HR = 1.998, p = 0.003). Accordingly, the time-independent receiver operating characteristic (ROC) curve confirmed that PITX1 had good predictive efficacy for OS and DSS. Meanwhile, a prediction model constructed by nomogram was used to predict the OS of KIRC patients, and the calibration plot indicated this model shows high accuracy. We also revealed some downstream target genes of PITX1-related signaling pathways. Our finding suggested that high PITX1 mRNA expression may act as an independent predictive factor of poor prognosis in patients with KIRC. The prognostic model based on the nomogram would be instrumental in evaluating the survival rate in KIRC patients.

Association between Inflammation and Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia.

PURPOSE: To evaluate the association between inflammation in prostatic tissue/serum sample and BPH-LUTS Patients and methods: The prostatic tissue and serum sample were collected from 183 patients who underwent transurethral plasmakinetic resection of the prostate (TUPKRP).  The association between inflammation detected on prostatic tissues/ serum sample and LUTS related parameters, including International Prostate Symptom Score (IPSS) and peak flow rate (Qmax) were analyzed with SPSS version 13.0, and P-value <0.05 was chosen as the criterion for statistical significance. RESULTS: There was a positive association between prostate tissue inflammation and LUTS. The differences of IPSS, VSS and SSS were seen with the increasing in grade of prostate tissue inflammation (P<.001; .001; =.014, respectively). Qmax and IPSS 12months after surgery were better in no inflammation group (P=.016; .031).Logistic regression analysis revealed a statistically association between the NEUT%?NLR and prostate tissue inflammation (P=.010; .004), but ROC curve showed the NEUT%, NEUT and NLR area under curve (.526; .452; .513, respectively) were calculated as <0.600. Patients with Qmax over 7.12 had more WBC count in peripheral blood (7.56±1.77 VS 6.37±1.86, P=.026). The NLR was significantly higher in the group of IPSS over 20 and AUR presence (P=.018; .017).The NEUT%, LYMPH%, LYMPH and NLR showed a statistically significance in different obstruction classification (P=.047; .046; .028; .014, respectively). CONCLUSION: There was correlation between chronic Inflammation and LUTS related to BPH. The patient without inflammation could acquire more sustained and steady relief than those with inflammation in LUTS related to BPH after TUPKRP.

Identification of potential core genes in metastatic renal cell carcinoma using bioinformatics analysis.

Most cases of mRCC without an early finding are not candidates for curative therapies, which may be one of the reasons for the poor patient prognosis. Therefore, candidate markers to diagnose the disease and treatment with high efficiency are urgently demanded. Three datasets of mRNA microarray have been assessed to discover DEGs between tissues from metastatic RCC and RCC. 111 DEGs in total were identified according to the expression profile result of genes in the database of GEO. Enrichment analyses for GO and KEGG have been conducted to reveal the interacting activities in the DEGs. A network of PPI has been established to reveal the interconnection among the DEGs, and we selected 10 hub genes. Subsequently, the disease-free survival rate and total survival rate analysis for the hub genes have been carried out with the method of Kaplan-Meier curve. RCC patients with CDH11, COL3A1, COL5A1, COL5A2, COL6A3 and COL11A1 alteration showed worse overall survival. Nonetheless, RCC patients with CDH11, COL3A1, COL5A1, COL5A2 and COL11A1 alteration showed worse disease-free survival. In the Jones Renal dataset, mRNA levels of 10 hub genes were associated with metastasis, and the gene expression level in patients with mRCC was higher than that in patients without metastasis. COL5A1, COL6A3 and COL11A1 expression levels were remarkably related to RCC patient survival rate using UALCAN. COL5A1, COL6A3 and COL11A1 were positively correlated with each other in RCC. These genes have been recognized as genes with clinical relevance, revealing that they might have important roles in carcinogenesis or development of mRCC.