Development and validation of two nomograms for predicting overall survival and Cancer-specific survival in prostate cancer patients with bone metastases: a population-based study.

BACKGROUND: Prostate cancer with bone metastasis has significant invasiveness and markedly poorer prognosis. The purpose of this study is to establish two nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) of prostate cancer patients with bone metastasis. METHODS: From January 2000 to December 2018, a total of 2683 prostate adenocarcinoma with bone metastasis patients were identified from the Surveillance, Epidemiology, and End Results Program (SEER) database. These patients were then divided into a training cohort and a validation cohort, with OS and CSS as the study endpoints. Correlation analyses were employed to assess the relationship between variables. Univariate and multivariate Cox analyses were utilized to ascertain the independent prognostic factors. Calibration curves and the area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were employed to evaluate discrimination and calibration of the nomogram. DCA was applied to examine accuracy and clinical benefits. The clinical utility of the nomogram and the AJCC Stage System was compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Lastly, the risk stratifications of the nomogram and the AJCC Stage System were compared. RESULTS: There was no collinearity among the variables that were screened. The results of multivariate Cox regression analysis showed that seven variables (age, surgery, brain metastasis, liver metastasis, lung metastasis, Gleason score, marital status) and six variables (age, surgery, lung metastasis, liver metastasis, Gleason score, marital status) were identified to establish the nomogram for OS and CSS, respectively. The calibration curves, time-dependent AUC curves, and DCA revealed that both nomograms had pleasant predictive power. Furthermore, NRI and IDI confirmed that the nomogram outperformed the AJCC Stage System. CONCLUSION: Both nomograms had satisfactory accuracy and were validated to assist clinicians in evaluating the prognosis of PABM patients.

Causes of death after testicular cancer diagnosis: a US population-based analysis.

BACKGROUND: After the introduction of cisplatin-based chemotherapy, the survival time of testicular cancer (TC) patients has improved dramatically. However, the overall risk of death in patients with TC remains significantly higher than in the general population. The aim of this study was to assess and quantify the causes of death after TC diagnosis. METHOD: In total, 44,975 men with TC in the United States diagnosed and registered by the Surveillance, Epidemiology, and End Results (SEER) database during 2000 to 2018 were studied. In this study, standardized mortality rates (SMRs) were calculated for each cause of death in TC individuals and further analyzed in strata according to age and race. RESULT: Of the included participants, 3,573 (7.94%) died during the follow-up period. The greatest proportion of deaths (38.20%) occurred within 1 to 5 years after diagnosis. Most deaths occurred from TC itself and other cancers. For non-malignant conditions, the most common causes of death within 1 years after diagnosis were accidents and adverse effects (53, 4.75%) followed by diseases of heart (45, 4.04%). However, > 1 years after diagnosis, the most common noncancer causes of death were heart diseases. Results of stratified analysis show that non-Hispanic White TC participants have a lower SMR (0.68, 95% CI, 33.39-38.67) from Cerebrovascular Diseases than the general U.S. CONCLUSIONS: Although TC remains the most common cause of death after TC diagnosis, other non-TC causes of death represent a significant number of deaths among TC men. These findings help TC survivors understand the various health risks that may occur at different follow-up periods.

lncRNA MIR4435-2HG promoted clear cell renal cell carcinoma malignant progression via miR-513a-5p/KLF6 axis.

Long non-coding RNAs (lncRNAs) take various biological effects in clear cell renal cell carcinoma (ccRCC) mostly through sponging with microRNAs (miRNAs). lncRNA MIR4435-2HG is found to promote tumour progression in gastric cancer, glioblastoma and hepatocellular carcinoma. However, the role of lncRNA MIR4435-2HG in ccRCC progression remains unknown. The purpose of this research was to investigate the potential molecular mechanism of lncRNA MIR4435-2HG regarding the regulation of ccRCC initiation and progression. In this study, we found the up-regulation of MIR4435-2HG in ccRCC tissues and cell lines. Functionally, overexpression of MIR4435-2HG promoted the proliferation as well as the metastasis in ccRCC cell lines, whereas knockdown of MIR4435-2HG inhibited the above changes. Then, bioinformatic analysis and luciferase reporter assays confirmed the negative regulation effect of MIR4435-2HG on miR-513a-5p. And further investigations showed that KLF6, which collected from the intersection of databases, was the potential conjugated mRNAs of miR-513a-5p. Finally, the rescue experiments revealed the relation among MIR4435-2HG and KLF6, which showed that KLF6 could reverse the promoting effect of MIR4435-2HG on ccRCC in vitro and in vivo. Therefore, our findings provided insight into the mechanisms of MIR4435-2HG in ccRCC and revealed an alternative target for the clinical diagnosis and treatment of ccRCC.

The management and composition of symptomatic seminal vesicle calculi: aetiological analysis and current research.

OBJECTIVE: To report our experience in the diagnosis, minimally invasive treatment, and composition of seminal vesicle calculi (SVC). PATIENTS AND METHODS: In the present study, we evaluated 20 patients who were admitted to our hospital from January 2013 to January 2018. All the patients were diagnosed with intractable haematospermia and SVC. The diagnosis was further confirmed by seminal vesiculoscopy. SVC were removed by basket extraction; with larger SVC fragmented by holmium laser before extraction. Scanning electron microscopy, X-ray diffraction, and infrared spectroscopy were used to determine the SVC composition. RESULTS: All operations were completed successfully without surgical complications. SVC were mostly composed of hydroxyapatite and protein, suggesting that they were produced by infections. CONCLUSIONS: Seminal vesiculoscopy is a simple, minimally invasive technique that can be used for diagnostic confirmation and treatment of seminal vesiculitis with SVC. This study improves our understanding of SVC and provides a theoretical basis for the prevention of postoperative recurrence of SVC.

Prognostic value of Lin28A and Lin28B in various human malignancies: a systematic review and meta-analysis.

BACKGROUND: The mammalian homologs of Lin-28, Lin28 (also called Lin28A) and Lin28B, are promising cancer biomarkers. This meta-analysis was performed to evaluate the prognostic values of Lin28A and Lin28B in multiple human malignancies. METHODS: Systematic searches of the PubMed, Web of Science and Embase were used to identify relevant studies. Pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS), or progression-free survival (PFS) were respectively calculated. RESULTS: 3772 Lin28A-associated patients and 1730 Lin28B-related cases were ultimately enrolled in this meta-analysis. The elevated expression level of Lin28A was significantly associated with poor OS (HR = 1.60, P < 0.001) and poor RFS/DFS/PFS (HR = 1.62, P < 0.001) in patients with malignancies. Lin28B overexpression significantly correlated with unfavorable OS (HR = 1.72, P < 0.001) and RFS/DFS/PFS (HR = 2.35, P < 0.001) of human malignancies. CONCLUSIONS: Lin28A and Lin28B possess significant prognostic values in various human malignancies. Overexpression of Lin28A or Lin28B suggests poor prognosis for cancer patients.

Application and analysis of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for patients with multiple renal tumor: initial experience.

BACKGROUND: To explore the feasibility and safety of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for the patients with multiple renal tumor of who have solitary kidney or contralateral kidney insufficiency. METHODS: Nine patients who have undergone retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping between October 2010 and January 2017 were retrospectively analyzed. Clinical materials and parameters during and after the operation were summarized. RESULTS: Nineteen tumors were resected in nine patients and the operations were all successful. The operation time ranged from 100 to 180 min (125 min); clamping time of segmental renal artery was 10 ~ 30 min (23 min); the amount of blood loss during the operation was 120 ~ 330 ml (190 ml); hospital stay after the operation is 3 ~ 6d (5d). There was no complication during the perioperative period, and the pathology diagnosis after the surgery showed that there were 13 renal clear cell carcinomas, two papillary carcinoma and four perivascular epithelioid cell tumors with negative margins from the 19 tumors. All patients were followed up for 3 ~ 60 months, and no local recurrence or metastasis was detected. At 3-month post-operation follow-up, the mean serum creatinine was 148.6 ± 28.1 µmol/L (p = 0.107), an increase of 3.0 µmol/L from preoperative baseline. CONCLUSIONS: For the patients with multiple renal tumors and solitary kidney or contralateral kidney insufficiency, retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping was feasible and safe, which minimized the warm ischemia injury to the kidney and preserved the renal function effectively.

H19-derived miR-675 contributes to bladder cancer cell proliferation by regulating p53 activation.

Long noncoding RNA 19 (H19) has been shown to promote bladder cancer cell proliferation and metastasis. However, little is known about how miR-675, mature product of H19, contributes to bladder cancer cell proliferation. In this study, we first evaluated the expression of miR-675 in bladder cancer tissues by quantitative real-time PCR (qRT-PCR) and defined its biological functions by flow cytometry and Western blotting. We found that miR-675 expression levels were remarkably increased in bladder cancer tissues as compared with adjacent noncancerous tissues or normal bladder tissue from health donors; moreover, enhanced miR-675 expression was also observed in bladder cancer cell lines. Ectopic expression of H19 significantly increased bladder cancer cell proliferation and miR-675 expression in vitro. Furthermore, overexpression of miR-675 promoted bladder cancer cell proliferation, while suppression of miR-675 induced G1 phase cell cycle arrest and promoted cell apoptosis. Western blotting analysis further identified that miR-675 inhibited p53 activation, decreased the ratio of Bax/Bcl-2 and cyclin D1 expression in bladder cancer cells; those effects may result in the abnormal proliferation of bladder cancer cells. In conclusion, abnormal enhanced miR-675 expression increases bladder cancer growth by regulating p53 activation, and thus may be helpful in the development of effective treatment strategies for bladder cancer.

Downregulation of tNASP inhibits proliferation through regulating cell cycle-related proteins and inactive ERK/MAPK signal pathway in renal cell carcinoma cells.

Nuclear auto-antigenic sperm protein (NASP), initially described as a highly auto-immunogenic testis and sperm-specific protein, is a histone chaperone that is proved to present in all dividing cells. NASP has two splice variants: testicular NASP (tNASP) and somatic form of NASP (sNASP). Only cancer, germ, transformed, and embryonic cells have a high level of expression of the tNASP. Up to now, little has been known about tNASP in renal cell carcinoma (RCC). In the present study, the molecular mechanism of tNASP in RCC was explored. The expression level of tNASP in 16 paired human RCC specimens was determined. Downregulation of tNASP by small interfering RNA (siRNA) was transfected in RCC cell lines. The effect of downregulation of tNASP by siRNA on cell colony formation and proliferation was examined by colony formation assay and CCK-8 assay, cell cycle was analyzed by flow cytometry, and the expression of cyclin D1 and P21 were detected by Western blotting. ERK/MAPK signaling was also analyzed. tNASP has a relative high expression level in human RCC tissues. Via upregulation of P21 and downregulation of cyclinD1, silence of tNASP can inhibit cell proliferation, which induces cell cycle arrest. Furthermore, ERK signaling pathway is confirmed to mediate the regulation of cell cycle-related proteins caused by silence of tNASP. Our research demonstrates that knockdown of tNASP effectively inhibits the proliferation and causes G1 phase arrest through ERK/MAPK signal pathway.

A novel surgical management for male infertility secondary to midline prostatic cyst.

BACKGROUND: To summary the procedure and experience of a novel surgical management for male infertility secondary to midline prostatic cyst (MPC). METHODS: From February 2012 to February 2014, 12 patients were diagnosed with PMC by semen analysis, seminal plasma biochemical analysis, transrectal ultrasonography (TRUS), and pelvic magnetic resonance imaging (MRI). All patients underwent the transurethral unroofing of MPC using resectoscope, the dilation of ejaculatory duct, and the irrigation of seminal vesicle using seminal vesiculoscope. All patients were followed up at least 3 months after operation. RESULTS: Preoperative semen analyses of 12 patients showed oligoasthenozoospermia (5/12) or azoospermia (7/12), low semen volume (0-1.9 mL), and low pH level (5.5-7.0). Preoperative seminal plasma biochemical analyses showed reduced semen fructose. TURS and MRI revealed a cyst lesion located in the midline of prostatic. After 3 months follow up, the semen quality of 80% patients (4/5) with oligoasthenozoospermia improved obviously. The spermatozoa were present in the semen in 5 of 7 cases with azoospermia. In one patient, the spermatozoa occurred in the urine after ejaculation. CONCLUSIONS: Surgical management using transurethral resectoscopy and seminal vesiculoscopy is effective, minimally invasive, and safe for male infertility secondary to MPC.

[Action mechanisms of prolactin and its receptors on penile erection and ejaculation].

Prolactin is a polypeptide hormone which mainly acts on the reproductive system and plays an important role in penile erection and ejaculation. Prolactin receptors have a variety of short forms apart from the classic long form, which are widely expressed in male reproductive glands. High levels of prolactin can induce erectile dysfunction and results in secondary male infertility, which are mainly associated with the inhibition of dopaminergic activity, reduction of the testosterone level, and contraction of the cavernous smooth muscle. Moreover, low levels of prolactin can result in ejaculatory dysfunction. This article updates the views on the expressions of prolactin receptors in the male reproductive system, the effects of prolactin on penile erection and ejaculation, and its action mechanisms.

[DAZL and male infertility: an update].

DAZL, a member of the DAZ family, plays a key role in human spermatogenesis. It regulates the promoter via genetic modification, especially DNA methylation, promoting the transcription of DAZL. Besides, the relation of DAZL SNPs with male infertility has been a hot spot of research for many years. It is deduced that local and ethnic factors may be associated with the failure of spermatogenesis. This article presents an overview on the results of recent studies, changes in the DNA methylation of DAZL in spermatogenesis, and the association of DAZL SNPs with male infertility, aiming to provide a new theoretical basis and clinical strategy for the treatment of male infertility.

Incremental value of radiomics with machine learning to the existing prognostic models for predicting outcome in renal cell carcinoma.

Purpose: To systematically evaluate the potential of radiomics coupled with machine-learning algorithms to improve the predictive power for overall survival (OS) of renal cell carcinoma (RCC). Methods: A total of 689 RCC patients (281 in the training cohort, 225 in the validation cohort 1 and 183 in the validation cohort 2) who underwent preoperative contrast-enhanced CT and surgical treatment were recruited from three independent databases and one institution. 851 radiomics features were screened using machine-learning algorithm, including Random Forest and Lasso-COX Regression, to establish radiomics signature. The clinical and radiomics nomogram were built by multivariate COX regression. The models were further assessed by Time-dependent receiver operator characteristic, concordance index, calibration curve, clinical impact curve and decision curve analysis. Result: The radiomics signature comprised 11 prognosis-related features and was significantly correlated with OS in the training and two validation cohorts (Hazard Ratios: 2.718 (2.246,3.291)). Based on radiomics signature, WHOISUP, SSIGN, TNM Stage and clinical score, the radiomics nomogram has been developed. Compared with the existing prognostic models, the AUCs of 5 years OS prediction of the radiomics nomogram were superior to the TNM, WHOISUP and SSIGN model in the training cohort (0.841 vs 0.734, 0.707, 0.644) and validation cohort2 (0.917 vs 0.707, 0.773, 0.771). Stratification analysis suggested that the sensitivity of some drugs and pathways in cancer were observed different for RCC patients with high-and low-radiomics scores. Conclusion: This study showed the application of contrast-enhanced CT-based radiomics in RCC patients, creating novel radiomics nomogram that could be used to predict OS. Radiomics provided incremental prognostic value to the existing models and significantly improved the predictive power. The radiomics nomogram might be helpful for clinicians to evaluate the benefit of surgery or adjuvant therapy and make individualized therapeutic regimens for patients with renal cell carcinoma.

Associations of waist circumference with sex steroid hormones among 4031 USA children and adolescents.

In the recent decades, obesity rates among children and adolescents, especially males, have increased significantly. This worldwide phenomenon is thought to significantly affect the levels of sex hormones. However, the association between waist circumference (a marker of abdominal obesity) and sex hormone levels in children and adolescents is unknown. In this study, 4031 participants aged 6-19 years from the United States National Health and Nutrition Examination Survey (NHANES) in the USA were enrolled in this study. The common confounders of age, race, body mass index, educational level, family income, diabetes, and time of sample collection were also collected. The participants missing any of the above information were excluded from the study. We used multiple linear regression and other multiple statistics to assess the associations between waist circumference and serum testosterone, estradiol, sex hormone-binding globulin (SHBG), free androgen index (FAI), and testosterone/estradiol ratio (T/E2). Waist circumference remained associated with sex hormone levels in children and adolescents after controlling for covariates. As waist circumference increases, testosterone levels in children and adolescents show an overall decline after a brief increase, with the inflection point for waist circumference of 65-66 cm. In addition, waist circumference positively correlates with estradiol levels in male children (ß = 0.007, 95% confidence interval: 0.004-0.009). Moreover, circulating SHBG decreases in children and adolescents as waist circumference increases. In conclusion, this study highlighted waist circumference as a vital indicator affecting sex hormone levels in children and adolescents.

Integrative analysis of triphenyl phosphate: contextual interpretation of bladder cancer cohort.

In recent years, organophosphate ester flame retardants (OPFRs) have emerged as preferred alternatives to brominated flame retardants (BFRs) in materials such as building supplies, textiles, and furnishings. Simultaneously, a notable surge in bladder cancer incidences has been observed globally, particularly in developed nations, placing it as the 10th most prevalent cancer type. Among the extensive OPFRs, the linkage between triphenyl phosphate (TPP) and bladder cancer remains inadequately investigated. Hence, our study endeavors to elucidate this potential association. We sourced transcriptome profiles and TPP-related data from The Cancer Genome Atlas and Comparative Toxicogenomics databases. Using the ssGSEA algorithm, we established TPP-correlated scores within the bladder cancer cohort. Differentially expressed analysis enabled us to identify key genes in bladder cancer patients. We utilized the LASSO regression analysis, along with univariate and multivariate COX regression analyses to construct a prognostic prediction model. To uncover critical pathways involving key genes, we employed GSEA and GSVA enrichment analyses. Molecular docking analysis was performed to determine the binding capability between TPP and proteins. Our findings reveal that the TPP-centric risk model offers valuable prediction for bladder cancer cohorts. Furthermore, the reliability of this TPP-influenced risk model was verified through ROC curve analysis and survival studies. Intriguingly, TPP exposure appears to bolster the proliferation and invasiveness of bladder cancer cells. This study furnishes new insights into the possible benefits of minimizing TPP exposure for hindering bladder cancer progression.

[Corrigendum] MicroRNA­379­5p plays a tumor­suppressive role in human bladder cancer growth and metastasis by directly targeting MDM2.

Following the publication of the above article, an interested reader drew to the authors' attention that the cell and invasion migration assay data featured in Figs. 2C and 5D contained two pairs of overlapping panels, such that the data appeared to have been derived from the same original sources, even though the data panels were intending to show the results from differently performed experiments. Moreover, there was also an instance of duplicated data panels comparing between the si­NC/cell invasion and si­NC/cell migration assay panels in Fig. 4C. After having examined their original data, the authors have realized that inadvertent errors were made during the process of compiling these figures. Corrected versions of Figs. 2, 4 and 5, incorporating all the data from one of the repeated experiments, are shown opposite and on the next page. The authors all agree to the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. They also regret any inconvenience caused to the readership of the Journal. [Oncology Reports 57: 3502­3508, 2017; DOI: 10.3892/or.2017.5607].

Integrative analysis of TRPV family to prognosis and immune infiltration in renal clear cell carcinoma.

The transient receptor potential vanilloid (TRPV) family has been preliminarily discovered to play an important role in various cancers, including clear cell renal cell carcinoma (ccRCC), which is closely associated with immune infiltration. However, the expression and prognosis of TRPV family and tumor-infiltrating immune cells in ccRCC are obscure. This study aimed to explore the prognostic and therapeutic value of the TRPV family expression in ccRCC from the perspective of bioinformatics. We analyzed the transcriptome and clinical data of kidney renal clear cell carcinoma (KIRC) from The Cancer Genome Atlas (TCGA) database. A clustering analysis and immune infiltration analysis were conducted to investigate the influence of the TRPV family genes on ccRCC. Our study found that the TRPV family is an excellent prognostic stratification for ccRCC. Among them, TRPV3 is the most significant prognostic marker of ccRCC. In addition, we performed a drug sensitivity analysis to identify the drugs with the strongest association with TRPV3. As a result, the TRPV family, particularly TRPV3, can act as a prognostic biomarker in ccRCC to determine prognosis and levels of immune infiltration.

Acinar with ductal and mucinous adenocarcinoma of prostate cancer complicated with lung metastasis: a case report and literature review.

Acinar adenocarcinoma, ductal adenocarcinoma and mucinous adenocarcinoma are the subtypes of prostate cancer (PCa). Most of the pathological types of PCa are acinar adenocarcinoma, while ductal adenocarcinoma and mucinous adenocarcinoma are uncommon. The case of acinar adenocarcinoma with ductal and mucinous adenocarcinoma has not been reported before. Herein, we report a treatment experience involving a 72-year-old man who presented similarly as most PCa patients, but the pathologic diagnosis was acinar adenocarcinoma with focal ductal and mucinous adenocarcinoma differentiating. Besides, this case is associated with lung metastasis, after radical prostatectomy (RP) and endocrine therapy the pulmonary nodule exerted a shrinking trend and the PSA level of this patient is still maintained at 0 ng/ mL till now. Through literature review, we found that patients who diagnosed as mixed pathological type of PCa had a lower survivor than pure PCa patients. Furthermore, there is no corresponding consensus or guideline for treating such multiple differentiated PCa patients. Surprisingly, this patient showed a high sensitivity to androgen deprivation therapy (ADT). Although the tumor presented aggressiveness, the followup results were satisfactory and we will continue to pay attention to his physical condition. We report this case to provide a treatment strategy for the patients with multi-differentiated PCa complicated with organ metastases.

Integrated Analysis of the Prognosis-Associated RNA-Binding Protein Genes and Candidate Drugs in Renal Papillary Cell Carcinoma.

RNA-binding proteins (RBPs) play significant roles in various cancer types. However, the functions of RBPs have not been clarified in renal papillary cell carcinoma (pRCC). In this study, we identified 31 downregulated and 89 upregulated differentially expressed RBPs on the basis of the cancer genome atlas (TCGA) database and performed functional enrichment analyses. Subsequently, through univariate Cox, random survival forest, and multivariate Cox regression analysis, six RBPs of SNRPN, RRS1, INTS8, RBPMS2, IGF2BP3, and PIH1D2 were screened out, and the prognostic model was then established. Further analyses revealed that the high-risk group had poor overall survival. The area under the curve values were 0.87 and 0.75 at 3 years and 0.78 and 0.69 at 5 years in the training set and test set, respectively. We then plotted a nomogram on the basis of the six RBPs and tumor stage with the substantiation in the TCGA cohort. Moreover, we selected two intersectant RBPs and evaluate their biological effects by GSEA and predicted three drugs, including STOCK1N-28457, pyrimethamine, and trapidil by using the Connectivity Map. Our research provided a novel insight into pRCC and improved the determination of prognosis and individualized therapeutic strategies.

Male reproductive toxicity of perfluorooctanoate (PFOA): Rodent studies.

Perfluorooctanoic acid (PFOA) is an artificial organic substance widely used for decades, which seriously threatens human health. This study aimed to identify human-relevant correlates between PFOA exposure and the male rodent reproductive system. We performed a systematic literature review of the relevant literature of PubMed, Cochrane Library databases, Web of Science and Embase from the establishment to April 2020. Studies included the effects of PFOA on the reproductive system of male rodents. The meta-analysis was performed on the basis of the following points: level of testosterone and estradiol in serum, development of reproductive organs, pathological changes of reproduction organs and parameters of semen. A series of 16 studies was enrolled in this study. The standard mean difference (SMD) for PFOA-related reproductive toxicity was summarised as -0.39 (95% confidence interval [CI]: 0.71, -0.07). The lower serum testosterone levels, decreased absolute testicular and epididymal weights, higher serum estradiol levels, elevated relative testicular and seminal vesicle weights and increased incidence of Leydig cell adenoma and percentage of abnormal sperm were observed in the exposed group compared with the control group. However, no statistical difference was found in the day of preputial separation of pups and percentage of motile sperm. In conclusion, PFOA exposure heightens the reproductive system damage in male rodents. However, many studies included in the review did not identify mechanisms by which PFOA induces changes to the male reproductive system, which is an area for additional study.

TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner.

BACKGROUND: Ubiquitylation modification is one of the multiple post-transcriptional process to regulate cellular physiology, including cell signaling, cycle regulation, DNA repair and transcriptional regulation. Members of TRIM family proteins could be defined as E3 ubiquitin ligases as they contain a RING-finger domain, and alterations of TRIM proteins are involved into a broad range of diverse disorders including cancer. TRIM37 is a novel discovered E3 ubiquitin ligase and acts as a oncoprotein in multiple human neoplasms, however its biological role in RCC still remains elusive. METHODS: RCC microarray chips and public datasets were screened to identify novel TRIMs member as TRIM37, which was dysregulated in RCC. Gain or loss of functional cancer cell models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Interactive network analyses were utilized to define intrinsic mechanism. RESULTS: We identified TRIM37 was upregulated in RCC tumors, and its aberrant function predicted aggressive neoplastic phenotypes, poorer survival endings. TRIM37 promoted RCC cells EMT and malignant progression via TGF-ß1 signaling activation, as a consequence of directly mediated by ubiquitinating-H2A modifications. CONCLUSIONS: Our findings identified a previously unappreciated role of TRIM37 in RCC progression and prognostic prediction. Importantly, we declared a novel ubiquitination-dependent link between TRIM ubiquitin ligases and TGF-ß1 signaling in regulating cancerous malignancies.