TIPARP as a prognostic biomarker and potential immunotherapeutic target in male papillary thyroid carcinoma.

BACKGROUND: Male patients with papillary thyroid carcinoma (PTC) tend to have poorer prognosis compared to females, partially attributable to a higher rate of lymph node metastasis (LNM). Developing a precise predictive model for LNM occurrence in male PTC patients is imperative. While preliminary predictive models exist, there is room to improve accuracy. Further research is needed to create optimized prognostic models specific to LNM prediction in male PTC cases. METHODS: We conducted a comprehensive search of publicly available microarray datasets to identify candidate genes continuously upregulated or downregulated during PTC progression in male patients only. Univariate Cox analysis and lasso regression were utilized to construct an 11-gene signature predictive of LNM. TIPARP emerged as a key candidate gene, which we validated at the protein level using immunohistochemical staining. A prognostic nomogram incorporating the signature and clinical factors was developed based on the TCGA cohort. RESULTS: The 11-gene signature demonstrated good discriminative performance for LNM prediction in training and validation datasets. High TIPARP expression associated with advanced stage, high T stage, and presence of LNM. A prognostic nomogram integrating the signature and clinical variables reliably stratified male PTC patients into high and low recurrence risk groups. CONCLUSIONS: We identified a robust 11-gene signature and prognostic nomogram for predicting LNM occurrence in male PTC patients. We propose TIPARP as a potential contributor to inferior outcomes in males, warranting further exploration as a prognostic biomarker and immunotherapeutic target. Our study provides insights into the molecular basis for gender disparities in PTC.

Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1.

Tumor-derived exosomes and their contents promote cancer metastasis. Phosphoglycerate mutase 1 (PGAM1) is involved in various cancer-related processes. Nevertheless, the underlying mechanism of exosomal PGAM1 in prostate cancer (PCa) metastasis remains unclear. In this study, we performed in vitro and in vivo to determine the functions of exosomal PGAM1 in the angiogenesis of patients with metastatic PCa. We performed Glutathione-S-transferase pulldown, co-immunoprecipitation, western blotting and gelatin degradation assays to determine the pathway mediating the effect of exosomal PGAM1 in PCa. Our results revealed a significant increase in exosomal PGAM1 levels in the plasma of patients with metastatic PCa compared to patients with non-metastatic PCa. Furthermore, PGAM1 was a key factor initiating PCa cell metastasis by promoting invadopodia formation and could be conveyed by exosomes from PCa cells to human umbilical vein endothelial cells (HUVECs). In addition, exosomal PGAM1 could bind to γ-actin (ACTG1), which promotes podosome formation and neovascular sprouting in HUVECs. In vivo results revealed exosomal PGAM1 enhanced lung metastasis in nude mice injected with PCa cells via the tail vein. In summary, exosomal PGAM1 promotes angiogenesis and could be used as a liquid biopsy marker for PCa metastasis.

Exposure to elevated temperature affects the expression of PIWI-interacting RNAs and associated transcripts in mouse testes.

BACKGROUND: Exposure to heat waves could result in adverse effects on human health, especially in male testicles. PIWI-interacting RNA (piRNA) is a novel type of small non-coding RNA, which can notably impact mRNA turnover and preserve germline maintenance in germline cells. However, piRNA's expression status when adapting to testicular heat stress remains largely unclear. OBJECTIVES: To investigate the function and mechanisms of relevant piRNAs during testicular heat stress. MATERIALS AND METHODS: In this study, a mouse testicular heat stress model was constructed, and the testes were removed for piRNA-sequencing. Bioinformatics analysis was used to discover the differential expressed piRNAs, piRNA clusters, and enriched pathways. A cell heat stress model was constructed to validate the top five upregulated piRNAs. Proliferation and apoptosis assays were utilized to validate the function of selected piRNA. Bioinformatics prediction, western blotting, and immunohistochemistry were used to illustrate the downstream mechanisms. RESULTS: Through the bioinformatics analysis, we identified the differential expression profile and enriched pathways of piRNAs and piRNA clusters during testicular hyperthermia. Besides, piR-020492 was proved to be upregulated in heat stress mouse testes and a germ cell model. A series of in vitro assays illustrated that an overexpression of piR-020492 could restrain the proliferation and promote the apoptosis of mouse germ cells. Kyoto Encyclopedia of Genes and Genomes analysis of piRNA-generating genes in the testicular heat stress model and piR-020492 targeting genes showed that the overlap pathways are adenosine monophosphate-activated protein kinase (AMPK) and insulin pathways. Validation experiments demonstrated that the key genes of AMPK and insulin pathway exhibit differential expression after an overexpression of piR-020492 or testicular heat stress. DISCUSSION AND CONCLUSION: In conclusion, our findings revealed the expression profile of piRNAs in testicular heat stress and illustrated the function and mechanisms of piR-020492 in germ cells, which could provide novel insights into the mechanism of hyperthermia-induced testicular injury.

Gut dysbiosis promotes prostate cancer progression and docetaxel resistance via activating NF-κB-IL6-STAT3 axis.

BACKGROUND: The gut microbiota is reportedly involved in the progression and chemoresistance of various human malignancies. However, the underlying mechanisms behind how it exerts some effect on prostate cancer, as an extra-intestinal tumor, in a contact-independent way remain elusive and deserve exploration. Antibiotic exposure, one of the various factors affecting the gut microbiota community and capable of causing gut dysbiosis, is associated with multiple disorders. This study aims to preliminarily clarify the link between gut dysbiosis and prostate cancer. RESULTS: First, we discovered that perturbing the gut microbiota by consuming broad-spectrum antibiotics in water promoted the growth of subcutaneous and orthotopic tumors in mice. Fecal microbiota transplantation could transmit the effect of antibiotic exposure on tumor growth. Then, 16S rRNA sequencing for mouse feces indicated that the relative abundance of Proteobacteria was significantly higher after antibiotic exposure. Meanwhile, intratumoral lipopolysaccharide (LPS) profoundly increased under the elevation of gut permeability. Both in vivo and in vitro experiments revealed that the NF-κB-IL6-STAT3 axis activated by intratumoral LPS facilitated prostate cancer proliferation and docetaxel chemoresistance. Finally, 16S rRNA sequencing of patients' fecal samples revealed that Proteobacteria was enriched in patients with metastatic prostate cancer and was positively correlated with plasma IL6 level, regional lymph node metastasis status, and distant metastasis status. The receiver operating characteristic (ROC) curves showed that the relative abundance of Proteobacteria had better performance than the prostate-specific antigen (PSA) level in predicting the probability of distant metastasis in prostate cancer (area under the ROC curve, 0.860; p < 0.001). CONCLUSION: Collectively, this research demonstrated that gut dysbiosis, characterized by the enrichment of Proteobacteria due to antibiotic exposure, resulted in the elevation of gut permeability and intratumoral LPS, promoting the development of prostate cancer via the NF-κB-IL6-STAT3 axis in mice. Considering findings from human patients, Proteobacteria might act as an intestinal biomarker for progressive prostate cancer. Video Abstract.

N6-methyladenosine demethylase FTO suppressed prostate cancer progression by maintaining CLIC4 mRNA stability.

The fat mass and obesity-associated protein (FTO) is an N6-Methyladenosine (m6A) demethylase, which has been revealed to play critical roles in tumorigenesis. However, its role in the development and progression of prostate cancer (PCa) remains poorly understood. Here, we aimed to investigate the function and clinical relevance of FTO in PCa. Our results demonstrated that FTO was notably downregulated in PCa tissues compared with the paired normal tissues. In addition, the decreased expression of FTO was correlated with poor prognosis of PCa. Functional experiments showed that depletion of FTO promoted the proliferation and metastasis of PCa both in vitro and in vivo. Conversely, ectopic expression of FTO exhibited the opposite effects. Combined with RNA-sequencing, MeRIP-RT-qPCR, and mRNA stability assays indicated chloride intracellular channel 4(CLIC4) was a functional target of FTO-mediated m6A modification. FTO depletion significantly increased the m6A level of CLIC4 mRNA and then reduced the mRNA stability. In conclusion, our findings suggest that FTO suppresses PCa proliferation and metastasis through reducing the degradation of CLIC4 mRNA in an m6A dependent manner. FTO may be used as a promising novel therapeutic target and prognostic evaluation biomarker for PCa.

Abrogation of HnRNP L enhances anti-PD-1 therapy efficacy via diminishing PD-L1 and promoting CD8+ T cell-mediated ferroptosis in castration-resistant prostate cancer.

Owing to incurable castration-resistant prostate cancer (CRPC) ultimately developing after treating with androgen deprivation therapy (ADT), it is vital to devise new therapeutic strategies to treat CRPC. Treatments that target programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for human cancers with clinical benefit. However, many patients, especially prostate cancer, fail to respond to anti-PD-1/PD-L1 treatment, so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy. In the present study, analyzing the data from our prostate cancer tissue microarray, we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L (HnRNP L). Hence, we further investigated the potential role of HnRNP L on the PD-L1 expression, the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC. Indeed, HnRNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo, on the contrary, HnRNP L overexpression led to the opposite effect in CRPC cells. In addition, consistent with the previous study, we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death, and HnRNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells. Furthermore, HnRNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8+ T cells and synergized with anti-PD-1 therapy in CRPC tumors. This study provided biological evidence that HnRNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.

LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer.

The interaction between LncRNA and RNA-binding protein (RBPs) plays an essential role in the regulation over the malignant progression of tumors. Previous studies on the mechanism of SNHG1, an emerging lncRNA, have primarily focused on the competing endogenous RNA (ceRNA) mechanism. Nevertheless, the underlying mechanism between SNHG1 and RBPs in tumors remains to be explored, especially in prostate cancer (PCa). SNHG1 expression profiles in PCa were determined through the analysis of TCGA data and tissue microarray at the RNA level. Gain- and loss-of-function experiments were performed to investigate the biological role of SNHG1 in PCa initiation and progression. RNA-seq, immunoblotting, RNA pull-down and RNA immunoprecipitation analyses were utilized to clarify potential pathways with which SNHG1 might be involved. Finally, rescue experiments were carried out to further confirm this mechanism. We found that SNHG1 was dominantly expressed in the nuclei of PCa cells and significantly upregulated in PCa patients. The higher expression level of SNHG1 was dramatically correlated with tumor metastasis and patient survival. Functionally, overexpression of SNHG1 in PCa cells induced epithelial-mesenchymal transition (EMT), accompanied by down-regulation of the epithelial marker, E-cadherin, and up-regulation of the mesenchymal marker, vimentin. Increased proliferation and migration, as well as accelerated xenograft tumor growth, were observed in SNHG1-overexpressing PCa cells, while opposite effects were achieved in SNHG1-silenced cells. Mechanistically, SNHG1 competitively interacted with hnRNPL to impair the translation of protein E-cadherin, thus activating the effect of SNHG1 on the EMT pathway, eventually promoting the metastasis of PCa. Our findings demonstrate that SNHG1 is a positive regulator of EMT activation through the SNHG1-hnRNPL-CDH1 axis. SNHG1 may serve as a novel potential therapeutic target for PCa.

Hyaluronic acid modified covalent organic polymers for efficient targeted and oxygen-evolved phototherapy.

The integration of multiple functions with organic polymers-based nanoagent holds great potential to potentiate its therapeutic efficacy, but still remains challenges. In the present study, we design and prepare an organic nanoagent with oxygen-evolved and targeted ability for improved phototherapeutic efficacy. The iron ions doped poly diaminopyridine (FeD) is prepared by oxidize polymerization and modified with hyaluronic acid (HA). The obtained FeDH appears uniform morphology and size. Its excellent colloidal stability and biocompatibility are demonstrated. Specifically, the FeDH exhibits catalase-like activity in the presence of hydrogen peroxide. After loading of photosensitizer indocyanine green (ICG), the ICG@FeDH not only demonstrates favorable photothermal effect, but also shows improved generation ability of reactive oxygen species (ROS) under near-infrared laser irradiation. Moreover, the targeted uptake of ICG@FeDH in tumor cells is directly observed. As consequence, the superior phototherapeutic efficacy of the targeted ICG@FeDH over non-targeted counterparts is also confirmed in vitro and in vivo. Hence, the results demonstrate that the developed nanoagent rationally integrates the targeted ability, oxygen-evolved capacity and combined therapy in one system, offering a new paradigm of polymer-based nanomedicine for tumor therapy.

MicroRNA miR-155-5p knockdown attenuates Angiostrongylus cantonensis-induced eosinophilic meningitis by downregulating MMP9 and TSLP proteins.

Angiostrongylus cantonensis infection is a major cause of eosinophilic meningitis (EM). Severe cases or cases that involve infants and children present poor prognoses. MicroRNAs (miRNAs), which are important regulators of gene expression in many biological processes, were recently found to be regulators of the host response to infection by parasites; however, their roles in brain inflammation caused by A. cantonensis are still unclear. The current study confirmed that miR-155-5p peaked at 21 days after A. cantonensis infection, and its expression was positively correlated with the concentration of excretory and secretory products (ESPs). We found that miR-155-5p knockdown lentivirus successfully ameliorated brain injury and downregulated the expression of major basic protein (MBP) in vivo, and the number of eosinophils in CSF (and the percentage of eosinophils in peripheral blood were also decreased in the miR-155-5p knockdown group. Moreover, the expression of several eosinophilic inflammation cytokines such as CCL6/C10, ICAM-1, and MMP9, declined after the miR-155-5p knockdown. SOCS1 protein, which is an important negative regulator of inflammation activation, was identified as a direct miR-155-5p target. We further detected the effect of miR-155-5p knockdown on phosphorylated-STAT3 and phosphorylated-p65 proteins, which were found to be negatively regulated by SOCS1 and play an important role in regulating the inflammatory response. We found that miR-155-5p knockdown decreased the activity of p-STAT3 and p-p65, thereby leading to lower expression of MMP9 and TSLP proteins, which were closely related to the chemotaxis and infiltration of eosinophils. Interestingly, the inhibition of p-STAT3 or p-p65 was found to induce the downregulation of miR-155-5p in an opposite manner. These observations suggest that a positive feedback loop was formed between miR-155-5p, STAT3, and NF-κB in A. cantonensis infection and that miR-155-5p inhibition might provide a novel strategy to attenuate eosinophilic meningitis.

Flubendazole, FDA-approved anthelmintic, elicits valid antitumor effects by targeting P53 and promoting ferroptosis in castration-resistant prostate cancer.

On account of incurable castration-resistant prostate cancer (CRPC) inevitably developing after treating with androgen deprivation therapy, it is an urgent need to find new therapeutic strategies. Flubendazole is a well-known anti-malarial drug that is recently reported to be a potential anti-tumor agent in various types of human cancer cells. However, whether flubendazole could inhibit the castration-resistant prostate cancer has not been well charified. Thus, the aim of the present study was to characterize the precise mechanism of action of flubendazole on the CRPC. In this study, we investigated the potential effect of flubendazole on cell proliferation, cell cycle and cell death in CRPC cells (PC3 and DU145). We found that flubendazole inhibited cell proliferation, caused cell cycle arrest in G2/M phase and promoted cell death in vitro, and suppressed growth of CRPC tumor in xenograft models. In addition, we reported that flubendazole induced the expression of P53, which partly accounted for the G2/M phase arrest and led to inhibition of the transcription of SLC7A11, and then downregulated the GPX4, which is a major ferroptosis-related gene. Furthermore, flubendazole exhibited synergistic effect with 5-fluorouracil (5-Fu) in chemotherapy of CRPC. This study provides biological evidence that flubendazole is a novel P53 inducer which exerts anti-proliferation and pro-apoptosis effects in CRPC through hindering the cell cycle and activating the ferroptosis, and indicates that a novel utilization of flubendazole in neoadjuvant chemotherapy of CRPC.

Pyrimethamine Elicits Antitumor Effects on Prostate Cancer by Inhibiting the p38-NF-κB Pathway.

Since incurable castration-resistant prostate cancer (CRPC) inevitably develops following treatment with androgen deprivation therapy, there is an urgent need to devise new therapeutic strategies to treat this cancer. Pyrimethamine, an FDA-approved antimalarial drug, is known to exert an antitumor activity in various types of human cancer cells. However, whether pyrimethamine can inhibit prostate cancer is not well established. Hence, the present study aimed to characterize the mechanism of action of pyrimethamine on prostate cancer. We investigated the potential effect of pyrimethamine on cell proliferation, cell cycle, and apoptosis in metastatic DU145 and PC3 prostate cancer cells. We found that pyrimethamine inhibited cell proliferation, induced cell cycle arrest in the S phase, and promoted cell apoptosis of prostate cells in vitro; it also suppressed tumor growth in xenograft models. In addition, we observed that pyrimethamine suppressed prostate cancer growth by inhibiting the p38-NF-κB axis in vitro and in vivo. Thus, this study demonstrates that pyrimethamine is a novel p38 inhibitor that can exert antiproliferative and proapoptotic effects in prostate cancer by affecting cell cycle and intrinsic apoptotic signaling, thereby providing a novel strategy for using pyrimethamine in CRPC treatment.

Microstructures of the spermatic cord with three-dimensional reconstruction of sections of the cord and application to varicocele.

The aim of the study was to investigate the micro-structures of the spermatic cord using histological examination with three-dimensional (3D) reconstruction of the serial tissue sections of the cord for clinical application in microscopic varicocelectomy. Human spermatic cord specimens obtained from 13 adult male cadavers were used to prepare serial transverse sections. The sections were stained to allow observation of the spermatic cord microstructures. The 3D reconstruction was performed with digitized serial sections by Mimics software. The microscopic varicocelectomy was performed based on the anatomical results of 3D reconstruction of the spermatic cord. The results showed the number of small spermatic veins, large spermatic veins, arteries, lymphatics or nerves were not markedly different between the subinguinal and inguinal regions or between the right and left sperm cord. The number of medium spermatic veins in the subinguinal region was obviously higher than at the inguinal level. The internal spermatic vessels and the vas deferens together with other associated vessels within the cremaster were separately enclosed by two thin and translucent sheaths, the internal spermatic fascia and the vas deferens fascia. We conclude that internal spermatic vessels and the vas deferens together with the associated neurovascular vessels are wrapped by two distinct sheaths separating them from the surrounding tissues. Microscopic varicocelectomy based on the anatomical results of 3D reconstruction of the spermatic cord is feasible. ABBREVIATIONS: 3D: three-dimensional; ISF: internal spermatic fascia; ESF: external spermatic fascia; MHIV: High inguinal microsurgical varicocelectomy; MSIV: subinguinal microsurgical varicocelectomy; CAAD: computer-assisted anatomic dissection; HE: hematoxylin-eosin.

Circular RNA CircNOLC1, Upregulated by NF-KappaB, Promotes the Progression of Prostate Cancer via miR-647/PAQR4 Axis.

BACKGROUND: CircRNAs recently have shown critical roles in tumor biology. However, their roles in prostate cancer (PCa) remains largely unclear. METHODS: CircRNA microarrays were performed in immortal prostate cell line RWPE1 and PCa cell lines as DU145, PC3, LNCaP, C4-2, and 22RV1. Combined with upregulated circRNAs in PCa tissues, circNOLC1 expression was validated in PCa cells and tissues via qRT-PCR and FISH. Sanger sequencing, actinomycin D, gDNA, and cDNA, RNase R assays were used to assess the circular characteristics of circNOLC1. CCK-8, colony formation, transwell migration assays, and mice xenograft models were conducted to evaluate the functions of PCa cells after circNOLC1 knockdown and overexpression. RNA pulldown, luciferase reporter assay, FISH (fluorescence in situ hybridization), and CHIP were utilized to illustrate the further mechanisms of circNOLC1. RESULTS: Our research indicated that circNOLC1 was overexpressed in PCa cells and tissues, and circNOLC1 was more stable than linear NOLC1 mRNA. CircNOLC1 promoted PCa cells proliferation and migration in vitro and vivo. Additionally, we found that circNOLC1 could upregulate PAQR4 expression by sponging miR-647, leading to the activation of PI3K/Akt pathway. Moreover, NF-kappaB was identified to bind to the NOLC1 promoter sites and upregulated both NOLC1 and circNOLC1 expression. CONCLUSION: CircNOLC1, elevated by transcription factor NF-kappaB, promotes PCa progression via a miR-647/PAQR4 axis, and circNOLC1 is a potential biomarker and target for PCa treatment.

Downregulation of lncRNA PVT1 expression inhibits proliferation and migration by regulating p38 expression in prostate cancer.

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) has been reported to be overexpressed in prostate cancer cells and associated with tumorigenesis in various types of cancer. However, the biological function of lncRNA PVT1 remains largely unknown. The aim of the present study was to investigate the effect of lncRNA PVT1 expression on the proliferation and migration of prostate cancer cells. Stably transfected prostate cancer cells with downregulated expression of lncRNA PVT1 were constructed by an efficient siRNA fragment, followed by confirmation by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Proliferation was assessed using CCK-8, colony formation and xenograft assays, and cell migration was evaluated using a wound healing assay. The PathScan® Intracellular Signaling Array kit was utilized to explore the underlying molecular mechanisms of lncRNA PVT1 expression in prostate cancer cells. RT-qPCR results confirmed that the lncRNA PVT1 expression level was successfully knocked down in prostate cancer cells. When lncRNA PVT1 expression was downregulated in prostate cancer cells, proliferation and migration were significantly inhibited, compared with the control lncRNA PVT1 group. Furthermore, PVT1 knockdown decreased the phosphorylation of p38 in DU145 cells. Therefore, the present study demonstrated that lncRNA PVT1 downregulation inhibits the proliferation and migration of prostate cancer cells, and is associated with p38 phosphorylation.

Flubendazole inhibits glioma proliferation by G2/M cell cycle arrest and pro-apoptosis.

Flubendazole, FDA-approved anthelmintic, has been widely used in treating testinal parasites. In the recent years, Flubendazole has been reported to exert anticancer activities. On the other hand, little was known about the effects of Flubendazole on gliomas. Here we demonstrated a novel effect of flubendazole on glioma cells. We found that Flubendazole inhibited cell proliferation and promoted cell apoptosis of glioma cell lines in vitro, and suppressed tumor growth in xenograft models by intraperitoneal injection. However, Flubendazole might have no influence on cell migration. Mechanism study reaveled that Flubendazole caused cell cycle arrest in G2/M phase, which partly account for the suppressed proliferation. Consistently, Flubendazole induced P53 expression and reduced Cyclin B1 and p-cdc2 expression in glioma cells. In addition, Flubendazole promoted cell apoptosis by regulating the classical apoptosis protein BCL-2 expression. These observations suggest that Flubendazole exerts anti-proliferation and pro-apoptosis effects in Glioma through affecting the cell cycle and intrinsic apoptotic signaling, and indicate a novel utilization of Flubendazole in the treatment of Glioma.

HnRNP-L mediates bladder cancer progression by inhibiting apoptotic signaling and enhancing MAPK signaling pathways.

Heterogeneous nuclear ribonucleoprotein L (hnRNP-L) is a promoter of various kinds of cancers, but its actions in bladder cancer (BC) are unclear. In this study, we investigated the function and the underlying mechanism of hnRNP-L in bladder carcinogenesis. Our results demonstrated that enhanced hnRNP-L expression in BC tissues was associated with poor overall survival of BC patients. Depletion of hnRNP-L significantly suppressed cell proliferation in vitro and inhibited xenograft tumor growth in vivo. Furthermore, downregulation of hnRNP-L resulted in G1-phase cell cycle arrest and enhanced apoptosis accompanied by inhibition of EMT and cell migration. All these cellular changes were reversed by ectopic expression of hnRNP-L. Deletion of hnRNP-L resulted in decreased expression of Bcl-2, enhanced expression of caspases-3, -6 and -9 and inhibition of the MAPK signaling pathway. These findings demonstrate that hnRNP-L contributes to poor prognosis and tumor progression of BC by inhibiting the intrinsic apoptotic signaling and enhancing MAPK signaling pathways.

HnRNP-L promotes prostate cancer progression by enhancing cell cycling and inhibiting apoptosis.

Expression of the RNA-binding protein HnRNP-L was previously shown to associate with tumorigenesis in liver and lung cancer. In this study, we examined the role of HnRNP-L in prostate cancer (Pca). We found that HnRNP-L is overexpressed in prostate tissue samples from 160 PC patients compared with tissue samples from 32 donors with cancers other than Pca. Moreover, HnRNP-L positively correlated with aggressive tumor characteristics. HnRNP-L knockdown inhibited cell proliferation and promoted cell apoptosis of Pca cell lines in vitro, and suppressed tumor growth when the cells were subcutaneously implanted in an athymic mouse model. Conversely, overexpression of HnRNP-L promoted cell proliferation and tumor growth while prohibiting cell apoptosis. HnRNP-L promoted cell proliferation and tumor growth in Pca in part by interacting with endogenous p53 mRNA, which was closely associated with cyclin p21. In addition, HnRNP-L affected cell apoptosis by directly binding the classical apoptosis protein BCL-2. These observations suggest HnRNP-L is an important regulatory factor that exerts pro-proliferation and anti-apoptosis effects in Pca through actions affecting the cell cycle and intrinsic apoptotic signaling. Thus HnRNP-L could potentially serve as a valuable molecular biomarker or therapeutic target in the treatment of Pca.

Analysis of the correlation of CATSPER single nucleotide polymorphisms (SNPs) with idiopathic asthenospermia.

PURPOSE: Idiopathic asthenospermia is the most common type of male infertility. Although the mechanisms causing asthenospermia are complex, recent studies have indicated an important role of cation channel of sperm (CATSPER) gene downregulation or abnormality in the etiology of idiopathic asthenospermia. METHODS: In the present study, 192 patients with idiopathic asthenospermia and 288 healthy controls were enrolled, and a flight mass spectrometry using Sequenom's MassArray biochip system was applied for genotyping 16 CATSPER gene SNPs reported in the human single nucleotide polymorphism (SNP) database. RESULTS: Our results indicated a correlation between CATSPER1 SNPs and idiopathic asthenospermia. In particular, the exonal SNP rs1893316 in CATSPER1 significantly correlated with idiopathic asthenospermia risk and is a potential important factor in determining an individual's genetic susceptibility to idiopathic asthenospermia. CONCLUSION: These finding will help to further elucidate the role of CATSPER1 in idiopathic asthenospermia pathogenesis.