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Background Cystoscopy plays an important role in bladder cancer (BCa) diagnosis and treatment, but its sensitivity needs improvement. Artificial intelligence has shown promise in endoscopy, but few cystoscopic applications have been reported. We report a Cystoscopy Artificial Intelligence Diagnostic System (CAIDS) for BCa diagnosis. Methods In total, 69 204 images from 10 729 consecutive patients from 6 hospitals were collected and divided into training, internal validation, and external validation sets. The CAIDS was built using a pyramid scene parsing network and transfer learning. A subset (n = 260) of the validation sets was used for a performance comparison between the CAIDS and urologists for complex lesion detection. The diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values and 95% confidence intervals (CIs) were calculated using the Clopper-Pearson method. Results The diagnostic accuracies of the CAIDS were 0.977 (95% CI = 0.974 to 0.979) in the internal validation set and 0.990 (95% CI = 0.979 to 0.996), 0.982 (95% CI = 0.974 to 0.988), 0.978 (95% CI = 0.959 to 0.989), and 0.991 (95% CI = 0.987 to 0.994) in different external validation sets. In the CAIDS vs urologists’ comparisons, the CAIDS showed high accuracy and sensitivity (accuracy = 0.939, 95% CI = 0.902 to 0.964; sensitivity = 0.954, 95% CI = 0.902 to 0.983) with a short latency of 12 seconds, much more accurate and quicker than the expert urologists. Conclusions The CAIDS achieved accurate BCa detection with a short latency. The CAIDS may provide many clinical benefits, from increasing the diagnostic accuracy for BCa, even for commonly misdiagnosed cases such as flat cancerous tissue (carcinoma in situ), to reducing the operation time for cystoscopy.

BACKGROUND and OBJECTIVE: A better understanding of the molecular mechanisms underlying bladder cancer is necessary to identify candidate therapeutic targets. METHODS: We screened for genes associated with bladder cancer progression and prognosis. Publicly available expression data were obtained from TCGA and GEO to identify differentially expressed genes (DEGs) between bladder cancer and normal bladder tissues. Weighted co-expression networks were constructed, and Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Associations between hub genes and immune infiltration and immune therapy were evaluated. RESULTS: 3461 DEGs in TCGA-BC and 1069 DEGs in the GSE dataset were identified, with 87 overlapping differentially expressed genes between the bladder cancer and normal bladder groups. Hub genes in the tumour group were mainly enriched for cell proliferation-related GO terms and KEGG pathways, while hub genes in the normal group were related to the synthesis and secretion of neurotransmitters. PPI networks for the genes identified in the normal and tumour groups were constructed. Based on a survival analysis, CDH19, RELN, PLP1, and TRIB3 were significantly associated with prognosis (P < 0.05). Four hub genes were significantly enriched in the MAPK signalling pathway, VEGF signalling pathway, WNT signalling pathway, cell cycle, and P53 signalling pathway based on a gene set enrichment analysis; these genes were associated with immune infiltration levels in bladder cancer. CONCLUSIONS: CDH19, RELN, PLP1, and TRIB3 may play important roles in the development of bladder cancer and are potential therapeutic and prognostic targets.

Background KCNJ15 belongs to the inwardly rectifying potassium channel (KIR) family. Although members of the KIR family have been proven to play important roles in a variety of developmental processes, the molecular role and clinical effects of KCNJ15 in cancers remain unclear. Purpose The aim of this study was to identify the expression, biological functions and molecular mechanisms of KCNJ15 in renal cell carcinoma (RCC). Methods KCNJ15 mRNA expression was evaluated in kidney cancer tissue, paired adjacent normal tissue, and cell lines with qRT-PCR. KCNJ15 protein expression was investigated via western blotting and immunohistochemistry. In addition, the clinical and prognostic significance of KCNJ15 in RCC were assessed using Kaplan-Meier analysis and Cox proportional hazards analysis. In vitro, the effects of KCNJ15 on kidney cancer cells were evaluated by means of a cell counting kit-8, transwell assay along with flow cytometry, respectively. Moreover, the potential mechanism of KCNJ15 was demonstrated by Western blot. Results Here, we first found that KCNJ15 was significantly downregulated in RCC, and this low expression was an independent prognostic factor for clear cell RCC (ccRCC). Moreover, KCNJ15 was associated with advanced TNM stage (n=150, p=0.014) and histological grade (n=150, p=0.045). Furthermore, KCNJ15 overexpression significantly inhibited RCC cell proliferation, migration, and colony formation, arrested the cell cycle and induced apoptosis of RCC cells in vitro. The inhibitory effect of KCNJ15 overexpression may be regulated by its effects on the epithelial mesenchymal transition (EMT) process and matrix metalloproteinase (MMP)-7 and p21 expression. Conclusion These findings indicate that KCNJ15 may be a tumor suppressor in RCC and a possible target for RCC therapy.

Aim: it has been reported that metastasis-associated lung adenocarcinoma transcript 1 is abnormally expressed in various cancers. Methods: eligible studies fulfilling the search criteria were selected from the online databases. Statistical analysis was performed based on the platforms of STATA 14.0. Results: 12 studies were included in this study comprising 741 cases and 794 controls. The pooled results were shown as follows: sensitivity, 0.74 (95% CI: 0.64–0.82), specificity, 0.83 (95% CI: 0.75–0.88), positive likelihood ratio (PLR), 4.2 (95% CI: 3.00–5.90), negative likelihood, 0.32 (95% CI: 0.23–0.43), diagnostic odds ratio, 13 (95%CI: 8.00–21.00) and area under the curve, 0.85 (95%CI: 0.82–0.88). Deeks’ funnel plot asymmetry test (p = 0.70) suggested no potential publication bias. Conclusion: long noncoding RNA Metastasis-associated lung adenocarcinoma transcript 1 might be a usable biomarker for cancer diagnosis and detection.

The current study is to investigate the expression pattern and biological function of long non-coding RNA Focally gastric cancer-associated transcript3 (GACAT3) in bladder cancer. Real-time quantitative qPCR was used to detect the expression level of GACAT-3 in tumor tissues and paired normal tissues. Human bladder cancer T24 and 5637 cell lines were transiently transfected with specific CRISPR-Cas13 or negative control CRISPR-Cas13. Cell migration, proliferation, and apoptosis were measured by using wound healing assay CCK-8 assay and Caspase-3 ELISA assay, respectively. The expression changes of p21, Bax, and E-cadherin after knockdown of GACAT3 were detected by using Western blot. The results demonstrated that GACAT3 was up-regulated in bladder cancer tissues than that in the paired normal tissues. Inhibition of cell proliferation, increased apoptosis, and decreased motility were observed in T24 and 5637 cell lines transfected by CRISPR-Cas13 targeting GACAT3. Downregulation of GACAT3 increased p21, Bax, and E-cadherin expression and silencing these genes could eliminate the phenotypic changes induced by knockdown of GACAT3. A ceRNA mechanism for GACAT3 was also revealed. By using CRISPR-Cas13 biotechnology, we suggested that GACAT3 may be a novel target for diagnosis and treatment of bladder cancer.

To compare the erectile function and urinary continence of patients after single-port transvesical laparoscopic radical prostatectomy (STLRP) with intrafascial endoscopic extraperitoneal radical prostatectomy (IEERP).Patients treated with STLRP (35) or IEERP (52) were recruited from September 2013 to June 2017. At baseline preoperatively and 2-year follow-up postoperatively, sex and continence assessments were performed by International Index of Erectile Function-6 (IIEF-6) and daily pads, respectively.The sexual function at 3 months after RP declined obviously. 71.4% (STLRP) and 38.5% (IEERP) patients recovered potency at 6 months postoperatively (P.01). 82.9% (STLRP) and 59.6% (IEERP) patients recovered potency at 2 years postoperatively (P.05). 97.1% (STLRP) and 75.0% (IEERP) patients recovered continence (0 pad/day) at 3 months postoperatively (P.01). Continence achieved 100.0% at 2 years after RP in both groups.Patients receiving STLRP may obtain better and faster postoperative functional recovery than the ones receiving IEERP. As an exploratory research, STLRP may be another effective treatment for organ-confined prostate cancer.

Objectives MUTYH is a protein-coding gene that takes part in base excision repair. Many previous studies have reported that MUTYH is directly related to hereditary adenomatous polyposis and colorectal cancer and is also associated with other cancers. However, the relationship between MUTYH and bladder cancer (BC) is unknown. Materials and methods The expression of MUTYH and clinical characteristics of BC were collected from databases including The Cancer Genome Atlas and Cancer Cell Line Encyclopedia. RNA sequencing and quantitative real-time PCR were used to detect MUTYH expression in SW780 BC cells. The level of MUTYH was stably downregulated by lentivirus-mediated vector in SW780 cells. Cell proliferation was evaluated using Cell Counting Kit-8 assay and 5-ethynyl-20-deoxyuridine assay, migration was detected using scratch assay and Transwell assay, and apoptosis was determined using ELISA. Results MUTYH was upregulated in BC tissues and SW780 cells and its expression level was positively associated with the stage and grade of carcinomas. MUTYH was successfully downregulated in SW780 cells by transducing with a lentivirus-mediated shRNA targeting MUTYH. MUTYH knockdown inhibited the proliferation and migration and induced apoptosis in SW780 cells. Conclusion Our data suggest that MUTYH is a new participant in bladder urothelial carcinoma. MUTYH may play a role as a biomarker and therapeutic target in BC.

Enhancer RNAs (eRNAs), a subclass of noncoding RNA from enhancers, have biological functions in gene expression. However, their potential role in bladder cancer (BCa) remains largely unknown. The present study investigated the functional role of androgen-associated androgen receptor (AR) mediated-eRNA MARC1 (eMARC1) in BCa progression. Cell proliferation, migration, and apoptosis of BCa cell lines (5637 and T24) with different eMARC1 expression levels or treated with 5α-dehydrotestosterone (DHT) were investigated. In the current study, we discovered that eMARC1 was highly expressed in BCa tissues and cell lines, and eMARC1 overexpression promoted the progression of BCa cells, while knockdown of eMARC1 suppressed tumorigenesis. DHT treatment significantly elevated eMARC1 expression levels, which also facilitated cell proliferation, motility, and inhibited cell apoptosis. We further found that eMARC1 silencing impaired the androgenic effect of DHT in BCa cells. These results suggested that eMARC1 exerted its effects on BCa cell progression, and DHT promoted bladder cancer progression by activating eMARC1.

Accumulating evidences indicate that long non-coding RNAs (lncRNAs) are indispensable in cancer initiation and progression. Dysregulation of functional lncRNAs can promote the development of cancers. Previous research have revealed that augmented expression of CRNDE caused poor prognosis of cancer patients and facilitate the tumor progress in various cancers. Nevertheless, the underlying roles of CRNDE in bladder cancer progression are not entirely clear. To further identify the effects CRNDE in bladder cancer progression, we performed the gain and loss of function assay. In this work, we have presented evidence that CRNDE was significantly increased in bladder cancer, and overexpressed expression of CRNDE was positively related with advanced TNM stage of bladder cancer patients. In addition, in vitro experiments showed that CRNDE strengthened cell migration/proliferation and inhibited cell apoptosis in bladder cancer. To sum up, our results exhibited new understand into the role of lncRNA CRNDE in the development of bladder cancer.

Upper tract urothelial carcinomas (UTUCs) are rare entities that are usually diagnosed at advanced stages. Research on UTUC pathobiology and clinical management has been hampered by the lack of models accurately reflecting disease nature and diversity. In this study, a modified organoid culture system is used to generate a library of 25 patient‐derived UTUC organoid lines retaining the histological architectures, marker gene expressions, genomic landscapes, and gene expression profiles of their parental tumors. The study demonstrates that the responses of UTUC organoids to anticancer drugs can be identified and the model supports the exploration of novel treatment strategies. This work proposes a modified protocol for generating patient‐derived UTUC organoid lines that may help elucidate UTUC pathophysiology and assess the responses of these diseases to various drug therapies in personalized medicine.

Neuron-derived neurotrophic factor (NDNF) is a glycosylated, disulfide-bonded secretory protein that contains a fibronectin type III domain. NDNF has been identified as a neurotrophic factor; however, its role in carcinogenesis has not yet been identified. To investigate the expression and role of NDNF in carcinogenesis, the expression of NDNF in human Renal cell carcinoma (RCC) cell lines and tissues was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Cell proliferation was investigated using CCK-8 and colony formation assays, and the cell invasion and immigration capacity was evaluated using the transwell assay. The results demonstrated that NDNF expression was downregulated in RCC cell lines and RCC tissues. Restoring NDNF expression significantly inhibited the proliferation, migration and invasion of RCC cells. The study also demonstrated that the inhibitory effect of NDNF on invasive ability was mediated by suppressing the epithelial-mesenchymal transition (EMT) in RCC cells. NDNF may therefore be considered an important regulator of EMT in RCC progression and may represent a novel promising target for antimetastatic therapy.

Long noncoding RNAs (lncRNAs) have been reported to serve as diagnostic and prognostic biomarkers of cancers, which play vital roles in tumorigenesis and tumor progression. Several studies have been performed to explore diagnostic value of lncRNA H19 in cancer detection and diagnosis. However, there are still inconsistent results in diagnostic accuracy and reliability in individual studies. Therefore, the present study was performed to summarize the overall diagnostic performance of lncRNA H19 in cancer detection and diagnosis. A total of eight studies with 770 cases and 815 controls were included in this pooled analysis. The pooled diagnostic results were as follows: sensitivity, 0.69 (95%CI=0.62-0.76), specificity, 0.79 (95% CI=0.70-0.86), positive likelihood ratio (PLR), 3.31 (95%CI=2.29-4.78), negative likelihood (NLR), 0.39 (95%CI=0.31-0.49), diagnostic odds ratio (DOR), 8.53 (95%CI=4.99-14.60), and area under the curve (AUC), 0.79 (95%CI=0.76-0.83). Deeks’ funnel plot asymmetry test (P=0.13) suggested no potential publication bias. Our results indicated that lncRNA H19 had a relatively moderate accuracy in cancer detection and diagnosis. Further comprehensive prospective studies with large sample sizes are urgently required to validate our findings.

Supplemental material, Supplemental_Figures for Gelsolin-like actin-capping protein has prognostic value and promotes tumorigenesis and epithelial-mesenchymal transition via the Hippo signaling pathway in human bladder cancer by Lyu Zhaojie, Liu Yuchen, Chen Miao, Chen Yacun, Wu Shayi, He Anbang, Liao Xinhui, Zhang Meng, Wu Peipei, Mei Hongbing, Wang Feng, Cai Zhiming and Guan Xinyuan in Therapeutic Advances in Medical Oncology

// Anbang He 1,2,* , Rong Hu 1,* , Zhicong Chen 2,3,* , Xinhui Liao 1,* , Jianfa Li 2,3 , Dailian Wang 2,4 , Zhaojie Lv 1 , Yuchen Liu 1,2 , Feng Wang 1 and Hongbing Mei 1,2 1 Department of Urology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China 2 Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China 3 Shantou University Medical College, Shantou, Guangdong, China 4 Guangzhou Medical University, Guangzhou, Guangdong, China * These authors have contributed equally to this work Correspondence to: Feng Wang, email: // Hongbing Mei, email: // Keywords : UCA1, lncRNA, prognosis, survival, lymph node metastasis Received : July 15, 2016 Accepted : September 21, 2016 Published : October 04, 2016 Abstract Accumulating evidences indicated that UCA1 expression was up-regulated in various cancers, and high UCA1 expression was correlated with metastasis and prognosis. This meta-analysis collected all eligible studies and explored the relationships between UCA1 expression and lymph node metastasis (LNM) or overall survival (OS). Literature collection was performed by using electronic databases PubMed, Cochrane Library, and Web of Science (up to June 13, 2016). According to the inclusion and exclusion criteria, twelve studies were included in the meta-analysis. The result showed that high UCA1 expression was correlated with more LNM (OR=2.50, 95 %CI: 1.58-3.96, p

BACKGROUND Many epidemiology studies have indicated that polymorphisms in ICAM-1 are associated with a variety of cancers, but published data are contradictory and inconclusive. Therefore, we conducted the current meta-analysis to elaborate the effects of ICAM-1 polymorphisms (rs5491, rs3093030, rs281432, and rs1799969) on cancer susceptibility. MATERIAL AND METHODS We conducted a comprehensive literature search in PubMed, Web of Science, and Google Scholar. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between ICAM-1 polymorphisms and cancer susceptibility. RESULTS We enrolled 14 published case-control studies including 4608 cancer cases and 4913 controls. We found an increased susceptibility of cancer in polymorphism rs1799969 (C vs. T: OR=1.662, 95%CI=1.288-2.143, p=0141; CT vs. TT: OR=1.860, 95%CI=1.398-2.474, p=0.507; CC+CT vs. TT: OR=1.812, 95%CI=1.373-2.391, p=0.284) of ICAM-1 among the overall population. However, no association between polymorphisms rs5491, rs3093030, or rs281432 of ICAM-1 and cancer susceptibility was identified. In the stratification analysis by ethnicity, we identified an increased susceptibility for Asians in rs3093030 polymorphism (CC vs. TC+TT: OR=1.728, 95% CI=1.234-2.421, p=0.787). CONCLUSIONS Our results suggest that the ICAM-1 polymorphism rs1799969 is significantly associated with increased susceptibility to overall cancer. Further studies (preferably prospective) are warranted to validate these relationships.

Objectives MUTYH is a protein-coding gene that takes part in base excision repair. Many previous studies have reported that MUTYH is directly related to hereditary adenomatous polyposis and colorectal cancer and is also associated with other cancers. However, the relationship between MUTYH and bladder cancer (BC) is unknown. Materials and methods The expression of MUTYH and clinical characteristics of BC were collected from databases including The Cancer Genome Atlas and Cancer Cell Line Encyclopedia. RNA sequencing and quantitative real-time PCR were used to detect MUTYH expression in SW780 BC cells. The level of MUTYH was stably downregulated by lentivirus-mediated vector in SW780 cells. Cell proliferation was evaluated using Cell Counting Kit-8 assay and 5-ethynyl-20-deoxyuridine assay, migration was detected using scratch assay and Transwell assay, and apoptosis was determined using ELISA. Results MUTYH was upregulated in BC tissues and SW780 cells and its expression level was positively associated with the stage and grade of carcinomas. MUTYH was successfully downregulated in SW780 cells by transducing with a lentivirus-mediated shRNA targeting MUTYH. MUTYH knockdown inhibited the proliferation and migration and induced apoptosis in SW780 cells. Conclusion Our data suggest that MUTYH is a new participant in bladder urothelial carcinoma. MUTYH may play a role as a biomarker and therapeutic target in BC.

Revealing the gene regulation networks governing cancer initiation and development is necessary while it remains uncompleted. In recent years, enhancers have been reported to be widely transcribed, resulting in the generation of enhancer RNAs (eRNAs). Previous studies have reported that eRNAs are a subclass of long noncoding RNAs (lncRNAs), which play a critical role in gene regulation and cancer development. These eRNAs can promote enhancer-promoter (E-P) looping formation by binding to other protein factors or propel expression of downstream protein-coding gene. In this review, we have focused on the characteristics of eRNAs and illustrated the biological function and potential mechanism of eRNAs in regulating gene expression and cancer development.

Objectives To study the expression pattern of long non-coding RNA FGFR3 antisense transcript 1(FGFR3-AS1) and the cell proliferation inhibition, apoptosis, and motility changes induced by silencing FGFR3-AS1 in bladder cancer. Methods The differential expression levels of FGFR3-AS1 and FGFR3 in tumor tissues and paired normal tissues were determined using Real-Time qPCR in a total of 36 patients diagnosed with bladder cancer (urothelial carcinoma). Pearson's coefficient correlation was used for expression correlation assay. Expression differences of FGFR3-AS1 were analyzed according to grading and staging. FGFR3 protein was detected by western blot assay. Human bladder cancer T24 and 5637 cell lines were transiently transfected with FGFR3-AS1-specific siRNA or negative control siRNA. The cell proliferation changes of transfected bladder cancer cells were determined using CCK-8 assay. Apoptosis caused by knockdown of FGFR3-AS1 was evaluated using ELISA assay. Motility changes induced by knockdown of FGFR3-AS1 were measured using wound healing assay and transwell assay. Results Both FGFR3-AS1 and FGFR3 were overexpressed in bladder cancer tissues compared to matched normal tissues. They were also positively expressed in bladder cancer. FGFR3-AS1 expression levels were higher in high grade tumors than those in low grade tumors. FGFR3-AS1 expression levels were higher in invasive tumors than those in non-invasive tumors. Cell proliferation inhibition, increased apoptosis, and decreased motility were observed in FGFR3-AS1 siRNA-transfected T24 and 5637 cell lines. Conclusions FGFR3-AS1 plays an oncogenic role in human bladder cancer. Knockdown of FGFR3-AS1 may provide a potential new therapeutic approach to this disease.

// Jiangeng Yang 1, 2 , Yuchen Liu 1, 2 , Anbang He 1, 2, 3 , Yuhan Liu 1 , Jianting Wu 1 , Xinhui Liao 1 , Zhaojie Lv 1 , Feng Wang 1 and Hongbing Mei 1, 2 1 Department of Urology, Shenzhen Second People’s Hospital, Clinical Institute of Guangzhou Medical University, Shenzhen, China 2 Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China 3 Anhui Medical University, Anhui, China Correspondence to: Hongbing Mei, email: hbmei68@163.com Keywords: microRNA, urothelial carcinoma, cyclin-dependent kinase inhibitor 2B Received: December 28, 2016 Accepted: July 06, 2017 Published: August 03, 2017 ABSTRACT Background and Objectives: Hsa-miR-429 is increased in bladder cancer. Its roles in bladder cancer are poorly understood. Methods: The expression levels of hsa-miR-429 and cyclin-dependent kinase inhibitor 2B (CDKN2B) were determined using Real-Time qPCR in a total of 50 patients with bladder cancer. Bladder cancer T24 and 5637 cells were transfected CDKN2B siRNA or hsa-miR-429 mimic. CDKN2B expression levels after transfection were detected by Real-Time qPCR and Western blot assay respectively. Binding sites between hsa-miR-429 and 3’-untranslated region of CDKN2B were confirmed by Dual luciferase reporter assay. Cell proliferation was evaluated using MTT and EdU assays. Cell apoptosis was determined using ELISA assay. Results: Higher hsa-miR-429 expression levels were associated with higher tumor grade and stage. All patients with low hsa-miR-429 expression survived 5 years, while with high hsa-miR-429 expression, only 58% survived. Hsa-miR-429 and CDKN2B were inversely expressed in bladder cancer. Hsa-miR-429 mimic decreased the expression of CDKN2B at both mRNA and protein levels. The binding site was confirmed between hsa-miR-429 and 3’-untranslated region of CDKN2B. Up-regulation of hsa-miR-429 or down-regulation of CDKN2B promoted cell growth and decreased apoptosis. Conclusions: Our data suggest a mechanism for hsa-miR-429 to play oncogenic roles via inhibiting CDKN2B.

Potassium inwardly rectifying channel, subfamily J, member 15 (KCNJ15) belongs to the inwardly rectifying potassium channel (KIR) family. Although members of the KIR family have been proven to play important roles in a variety of developmental processes, the expression, biological functions and molecular mechanisms of KCNJ15 in cancers remain unclear. Here, we first found that KCNJ15 was significantly downregulated in renal cell carcinoma (RCC), and this low expression was an independent prognostic factor for clear cell RCC. Moreover, KCNJ15 was associated with advanced TNM stage (n=150, P=0.014) and histologic grade (n=150, P=0.045). Furthermore, KCNJ15 overexpression significantly inhibited RCC cell proliferation, migration, and colony formation, arrested the cell cycle and induced apoptosis of RCC cells in vitro. The inhibitory effect of KCNJ15 overexpression may be regulated by its effects on the epithelial mesenchymal transition process and matrix metalloproteinase (MMP)-7 and p21 expression. These findings indicate that KCNJ15 may be a tumour suppressor in RCC and a possible target for RCC therapy.

Human CMTM3 has been proposed as a putative tumor suppressor gene. The loss of CMTM3 has been found in several carcinomas. However, the regulation of CMTM3 expression and its function in tumor progression remain largely unknown. Here, we investigated the regulation of CMTM3 expression, function and molecular mechanism in human testicular cancer cells. CMTM3 was frequently downregulated or silenced in testicular cancer cell lines and tumor tissues but highly expressed in normal testis tissues. The re-expression of CMTM3 significantly suppressed the colony formation, proliferation, and migration capacity of testicular cancer cells by inducing a G2 cell cycle arrest and apoptosis. Moreover, the re-expression of CMTM3 activated the transcription of p53, induced p53 accumulation, up-regulated the expression of p21, and increased the cleavage of caspase 9, 8, 3, and PARP. The downregulation of CMTM3 in clinical tumor tissues was associated with the methylation of a single CpG site located within the Sp1/Sp3-responsive region of the core promoter. These results indicate that CMTM3 can function as tumor suppressor through the induction of a G2 cell cycle arrest and apoptosis. CMTM3 is thus involved in testicular cancer pathogenesis, and it is frequently at least partially silenced by the methylation of a single, specific CpG site in tumor tissues.

Meng Zhang,1,2,* Xiuxiu Tan,1,* Junjie Huang,3,* Lijuan Xie,1 Hao Wang,1 Jizhou Shi,4 Wei Lu,1 Zhaojie Lv,1 Hongbing Mei,1 Chaozhao Liang21Department of Urology, Shenzhen Second People’s Hospital, Clinical Medicine of Anhui Medical University, 2Department of Urology, the First Affiliated Hospital of Anhui Medical University, Hefei, 3Department of Hematology, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, 4Department of Urology, Shengli Oilfield Central Hospital, Dongying, Peoples Republic of China *These authors contributed equally tothis workBackground: Several epidemiological studies have illustrated that polymorphisms in interleukin-2 (IL-2) were associated with diverse cancer types. However, recently published statistics were inconsistent and inconclusive. Therefore, the current meta-analysis was performed to elaborate the effects of IL-2 polymorphisms (rs2069762 and rs2069763) on cancer susceptibility.Material and methods: A total of 5,601 cancer cases and 7,809 controls from 21 published case–control studies were enrolled in our meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between IL-2 polymorphisms and cancer susceptibility.Results: Our study demonstrated an increased susceptibility to cancer in rs2069762 (G vs T: OR =1.268, 95% CI =1.113–1.445; GG vs TT: OR =1.801, 95% CI =1.289–2.516; GT vs TT: OR =1.250, 95% CI =1.061–1.473; GG + GT vs TT: OR =1.329, 95% CI =1.118–1.579; GG vs GT + TT: OR =1.536, 95% CI =1.162–2.030). In the subgroup analysis, increased susceptibility to cancer was identified in the hospital-based group and PHWE