Abstract Background Circular RNAs (circRNAs) are those RNA molecules that lack the poly (A) tails, which present the closed-loop structure. Recent studies emphasized that some circRNAs imply different functions from canonical transcripts, and further associated with complex diseases. Several computational methods have been developed for detecting circRNAs from RNA-seq data. However, the existing methods prefer to high sensitivity strategies, which always introduce many false positives. Thus, in clinical decision-supporting system, a comprehensive filtering approach is needed for accurately recognizing real circRNAs for decision models. Methods In this paper, we first reviewed the detection strategies of the existing methods. According to the features from RNA-seq data, we showed that any single feature (data signal) selected by the existing strategies cannot accurately distinguish a circRNA. However, we found that some combinations of those features (data signals) could be used as signatures for recognizing circRNAs. To avoid the high computational complexity of the combinational optimization problem, we present CIRCPlus2, which adopts a machine learning framework to recognize real circRNAs according to multiple data signals captured from RNA-seq data. By comparing multiple machine learning frameworks, CIRCPlus2 adopts a Gradient Boosting Decision Tree (GBDT) framework. Results Given a set of candidate circRNAs, reported by any existing detection tool(s), the features of each candidate are extracted from the aligned reads. The GBDT framework can be trained by a training dataset. By applying the selected features on the framework, the predictions on true/false positives are reported. To verify the performance of the proposed approach, we conducted several groups of experiments on both real RNA-seq datasets and a series of simulation datasets with different preset configurations. The results demonstrated that CIRCPlus2 clearly improved the specificities, while it also maintained high levels of sensitivities. Conclusions Filtering false positives is quite important in RNA-seq data analysis pipeline. Machine learning framework is suitable for solving this filtering problem. CIRCPlus2 is an efficient approach to identify the false positive circRNAs from the real ones.
We aimed to investigate the pivotal role of Tripartite Motif Containing 66 (TRIM66) in bladder cancer (BCa) and elucidate its underlying mechanism in promoting BCa cell metastasis. Tumor and adjacent normal tissues were collected from 62 BCa patients, and TRIM66 was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between TRIM66 expression and clinical indicators, as well as patient prognosis, was analyzed. In addition, an in vitro model was established by silencing TRIM66 in a BCa cell line. The impact of TRIM66 on BCa cell invasion and metastasis was evaluated through Transwell and cell wound healing assays. Through meticulous bioinformatics analysis and luciferase assays, we confirmed that TRIM66 specifically binds to Matrix Metallopeptidase 11 (MMP11). Moreover, mRNA expression analysis revealed a positive correlation between TRIM66 and MMP11 in BCa tumor tissues. Intriguingly, in a cell recovery experiment, overexpression of MMP11 reversed the inhibition of migration and proliferation caused by TRIM66 downregulation. Collectively, our findings unequivocally indicate that heightened TRIM66 expression is closely associated with a malignant phenotype in BCa tissues. Silencing TRIM66 significantly mitigates BCa cell metastasis in vitro by downregulating MMP11. These observations shed light on the critical involvement of the TRIM66-MMP11 axis in BCa progression, offering promising avenues for therapeutic interventions targeting this pathway.
Objective To discuss the clinical and pathological features of the juvenile xanthogranuloma of testis.Methods A case of the juvenile xanthogranuloma of testis was reported.A 6-month-old boy presented with scrotal mass for 2 weeks before admission.Physical examination revealed that the left testis was hard with the size of 2.0 cm×2.0 cm and the serum alpha-fetoprotein was 37.60 μg/L.Chest X-ray and serum human chorionic gonadotropin investigations were normal.B-ultrasound examination showed a solid mass of uniform homogeneity in the left testis,with rich blood supply.Results The patient underwent operation after inguinal incision under general anaesthesia.During operation the left spermatic was augmented,and the mass was infiltrated into the whole testis and epididydis,and an inguinal orchiectomy was competed.Histopathological examination revealed that the lesion was intratesticular and involvement of the epididymis,predominantly occupied with an infiltrative pattern of by mononuclear cells,foamy cells and inflammatory cells (neutrophils,eosinophils,lymphocytes),without Touton giant cells.Immunohistochemical examination revealed positive for CD68 and CD163,and negative for CD1a.The pathological result was juvenile xanthogranuloma.During the follow-up period for 10 months,no recurrence was recorded.Conclusions Juvenile xanthogranuloma of the testis is an extremely rare benign disease lack of special feature in clinical manifestation.The diagnosis mainly depends on histological features and special markers in immunohistochemistry.Differential diagnosis should be made among leukemia,lymphoma and other distinctive neoplasms.
Key words:
Testicular neoplasms; Juvenile xanthogranuloma; Pathology, clinical
This study aimed to investigate the effect of over-expressing circular RNA CEP128 (circCEP128) on cell functions and explore the molecular mechanism of which in bladder carcinoma. The differentially expressed circRNAs and mRNAs in bladder carcinoma cells and cells in adjacent tissues were screened out using microarray analysis. Expression levels of circRNAs and mRNAs in tissues and cells were determined by qRT-PCR. Expression of SOX11 was detected by western blot. Luciferase reporter assay and RNA pull-down assay were used to investigate the interactions between the specific circRNA, miRNA and mRNA. Cell cycle and apoptosis were measured using flow cytometry after transfection. MTT assay was also performed to detect the cell proliferation. In present study, circCEP128 and SOX11 were observed significantly up-regulated in bladder cancer tissues, while the expression of miR-145-5p was decreased in cancer samples compared to normal samples. Cytoscape was used to visualize circCEP128-miRNA-target gene interactions based on the TargetScan and circular RNA interactome, which revealed that circCEP128 served as a sponge of miR-145-5p and indirectly regulated SOX11. Knockdown of circCEP128 induced the inhibition of cell proliferation and the increased bladder cancer cell apoptosis rate. CircCEP128 functions as a ceRNA for miR-145-5p, which could up regulates SOX11 and further promotes cell proliferation and inhibits cell apoptosis of bladder cancer.
Background It has been reported that the functional telomerase reverse transcriptase (TERT) rs2853669 polymorphism might contribute to different types of human cancer. However, the association of this mutation with cancer remains controversial. Here, we conducted a meta-analysis to characterize this relationship. Materials and methods/Main results A systematic search of studies on the association of TERT rs2853669 polymorphism with all types of cancer was conducted in PubMed, Embase and Cochrane Library. The summary odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used to pool the effect size in a fixed-effects model or a random-effects model where appropriate. A total of 13 articles and 15 case-control studies, including 9,157 cases and 11,073 controls, were included in this meta-analysis. Overall, the pooled results indicated that the rs2853669 polymorphism was significantly associated with increased cancer risk in a homozygote comparison model (CT vs. TT: OR = 1.085, 95% CI: 1.015–1.159, P = 0.016). In the stratified analyses, a significant increased cancer risk was observed in Asian, but not Caucasian patients. A subgroup analysis by cancer type also revealed a significant increase in the risk of lung cancer, but not breast cancer. Conclusions The results of this meta-analysis suggest that the TERT rs2853669 polymorphism is associated with a significantly increased risk of cancer, particularly lung cancer, in Asian populations.
miR-489-3p Inhibits Prostate Cancer Progression by Targeting DLX1 Peide Bai,1 Wei Li,1 Zhenghua Wan,2 Yujuan Xiao,3 Wen Xiao,1 Xuegang Wang,1 Zhun Wu,1 Kaiyan Zhang,1 Yongfeng Wang,1 Bin Chen,1 Jinchun Xing,1 Tao Wang1 1The Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology Surgery, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361003, People's Republic of China; 2Xiang'an Branch, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361101, People's Republic of China; 3Department of Pediatrics, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361003, People's Republic of ChinaCorrespondence: Jinchun Xing; Tao WangThe First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, People's Republic of ChinaTel/Fax +86-592-2139814; +86-592-2137125Email xmcua2007@sina.com; taowang@xmu.edu.cnPurpose: Prostate cancer (PCa) is the third most common cancer in men and the second leading cause of cancer-related death in men. DLX1 belongs to the DLX homeobox family and exhibits antitumor activity in many kinds of tumors. MicroRNAs (miRNAs) play important roles in the progression of cancer. However, whether miRNAs affect the development of PCa by targeting DLX1 has not been determined. In this study, we aimed to investigate the role of miR-489-3p in the regulation of DLX1 expression and PCa progression and to provide a potential therapeutic target for PCa treatment.Methods and Materials: The Cancer Genome Atlas database was used to analyze the divergent expression of DLX1 in carcinomas and adjacent normal tissues. The expression level of DLX1 in malignant and normal prostate cells was also measured using RT-qPCR and Western blotting. A dual-luciferase reporter assay was performed to determine whether miR-489-3p directly targets DLX1. We transfected 22Rv1 and DU145 cells with miR-489-3p mimics to overexpress miR-489-3p and then evaluated its effect on cellular function. MTT, EdU, colony formation and cell cycle assays were used to evaluate cell growth. JC-1 and ROS assays with flow cytometry were performed to indirectly analyze apoptosis. Transwell assays were conducted to investigate metastasis.Results: The expression level of DLX1 was upregulated in both PCa tissues and cell lines. MiR-489-3p directly targeted DLX1 and downregulated its expression. Overexpression of miR-489-3p significantly suppressed cell growth. MiR-489-3p induced apoptosis through mitochondrial function impairment. Overexpression of miR-489-3p also inhibited cell migration and invasion. DLX1 overexpression reversed the above effects induced by miR-489-3p.Conclusion: We identified the involvement of the miR-489-3p/DLX1 pathway in PCa for the first time. In this pathway, miR-489-3p acts as a tumor suppressor by negatively regulating the expression of DLX1. MiR-489-3p may be a potential therapeutic target for PCa treatment.Keywords: prostate cancer, DLX1, miR-489-3p, growth, apoptosis, migration, invasion
Patients with urothelial carcinoma (UC) of the bladder have a high risk of death in China. However, a lack of comprehensive molecular profiling in Chinese Han population hinders the development of targeted therapies for bladder cancer. In our present study, we collected fresh bladder tumors from low-grade (T1, N0, M0, G1) non-muscle invasive bladder cancer (NMIBC) patients (n = 16) and high-grade (T2-4, N0, M0, Gx) muscle-invasive bladder cancer (MIBC) patients (n = 16) with their paired normal bladder tissues, and subjected the total genomic DNAs to targeted next-generation sequencing (NGS) for 94 cancer-associated genes. NGS results showed that 30.9% of detected genes (29/94) was mutated in 32 urothelial carcinoma bladder tissues. Furthermore, our results and ICGC database showed that FGFR3, KMT2D, TP53, KDM6A, and ARID1A were the most frequently mutated genes in UC patients. Of note, NMIBC and MIBC displayed distinguishable genomic alterations. FGFR3, KMT2D, AKT1, ARID1A, and STAG2 were the most frequently mutated genes in NMIBC patients, whereas mutations of TP53, CREBBP, FGFR3, KDM6A, KMT2D, and ARID1A were frequently detected in MIBC. Intriguingly, gene ontology and clustering analysis revealed that these frequently mutated genes were highly enriched in signaling pathways responsible for cancer development. Taken together, the mutation frequency of genes associated with UC development in NMIBC and MIBC was screened out in Chinese Han population and elucidation of the related mechanisms provides theoretical basis and technical support for the development of early diagnosis and therapeutic strategies in UC.
To investigate current status of diagnosis and treatment of bladder cancer in China.A database was generated by Chinese Bladder Cancer Consortium (CBCC). From January 2007 to December 2012, 14,260 cases from 44 CBCC centers were included. Data of diagnosis, treatment and pathology were collected.The average age was 63.5 year-old and most patients were male (84.3%). The most common histologic types were urothelial carcinoma (91.4%), adenocarcinoma (1.8%), and squamous carcinoma (1.9%). According to 1973 and 2004 WHO grading system, 42.0%, 41.0%, and 17.0% of patients were grade 1, 2, and 3, and 16.0%, 48.7%, and 35.3% of patients were papillary urothelial neoplasms of low malignant potential, low, and high grade, respectively. Non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) were 25.2% and 74.1%, respectively (0.8% not clear). Carcinoma in situ was only 2.4%. Most patients were diagnosed by white-light cystoscopy with biopsy (74.3%). Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%, respectively. Diagnostic transurethral resection (TUR) provided detection rate of 16.9%. Most NMIBCs were treated with TUR (89.2%). After initial TUR, 2.6% accepted second TUR, and 45.7%, 69.9%, and 58.7% accepted immediate, induced, and maintenance chemotherapy instillation, respectively. Most MIBCs were treated with radical cystectomy (RC, 59.7%). Laparoscopic RCs were 35.1%, while open RC 63.4%. Extended and standard pelvic lymph node dissection were 7% and 66%, respectively. Three most common urinary diversions were orthotopic neobladder (44%), ileal conduit (31%), and ureterocutaneostomy (23%). Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18% of T3 and T4 patients accepted adjuvant chemotherapy.Disease characteristics are similar to international reports, while differences of diagnosis and treatment exist. This study can provide evidences for revisions of the guideline on bladder cancer in China.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)