Deep neural networks for human microRNA precursor detection.

BACKGROUND: MicroRNAs (miRNAs) play important roles in a variety of biological processes by regulating gene expression at the post-transcriptional level. So, the discovery of new miRNAs has become a popular task in biological research. Since the experimental identification of miRNAs is time-consuming, many computational tools have been developed to identify miRNA precursor (pre-miRNA). Most of these computation methods are based on traditional machine learning methods and their performance depends heavily on the selected features which are usually determined by domain experts. To develop easily implemented methods with better performance, we investigated different deep learning architectures for the pre-miRNAs identification. RESULTS: In this work, we applied convolution neural networks (CNN) and recurrent neural networks (RNN) to predict human pre-miRNAs. We combined the sequences with the predicted secondary structures of pre-miRNAs as input features of our models, avoiding the feature extraction and selection process by hand. The models were easily trained on the training dataset with low generalization error, and therefore had satisfactory performance on the test dataset. The prediction results on the same benchmark dataset showed that our models outperformed or were highly comparable to other state-of-the-art methods in this area. Furthermore, our CNN model trained on human dataset had high prediction accuracy on data from other species. CONCLUSIONS: Deep neural networks (DNN) could be utilized for the human pre-miRNAs detection with high performance. Complex features of RNA sequences could be automatically extracted by CNN and RNN, which were used for the pre-miRNAs prediction. Through proper regularization, our deep learning models, although trained on comparatively small dataset, had strong generalization ability.

Wogonin inhibits in vitro herpes simplex virus type 1 and 2 infection by modulating cellular NF-κB and MAPK pathways.

BACKGROUND: Wogonin, a natural flavonoid-like chemical compound, exhibits anti-inflammatory, antitumor, antiviral, neuroprotective, and anxiolytic effects by modulating a variety of cellular signaling pathways including PI3K-Akt, p53, nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK) pathways. In this study, its antiviral effect against herpes simplex virus (HSV) type 1 and 2 (HSV-1 and HSV-2) replication was investigated. RESULTS: Wogonin suppressed HSV-2-induced cytopathic effect (CPE) and reduced viral mRNA transcription, viral protein synthesis, and infectious virion particle titers in a dose-dependent manner. A time-of-drug-addition assay demonstrated that wogonin acted as a postentry viral inhibitor. Wogonin also significantly reduced HSV-induced NF-κB and MAPK pathway activation, which has previously been demonstrated to be important for viral replication. CONCLUSIONS: Our results suggest that the anti-herpes effect of wogonin may be mediated by modulation of cellular NF-κB and JNK/p38 MAPK pathways and imply that wogonin may be useful as an anti-HSV agent.

Red Cell Distribution Width as a Prognostic Factor in Patients with Hepatocellular Carcinoma.

BACKGROUND: The red blood cell distribution width (RDW) was reported to be related to the severity of liver diseases, but its clinical significance in patients with hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to explore the clinical significance of RDW in HCC patients. METHODS: For the retrospective study, 422 HCC patients were enrolled in this study. Hematological parameters and liver biochemical indexes were analyzed. Child-Pugh grade and Barcelona Clinic Liver Cancer (BCLC) stages of the HCC patients were calculated. The diagnostic accuracy was evaluated according to the area under the receiver operating characteristic (ROC) curve. The medical records of HCC patients who were admitted to The Second Affiliated Hospital of Nanjing University of Chinese Medicine from January 2006 to August 2015 were retro-spectively reviewed. RESULTS: Subgroup analysis showed that RDW level of HCC patients with tumor size more than 10 cm were higher than those of HCC patients with tumor size smaller than 3 cm, 3 - 5 cm, and 5 - 10 cm (14.77 ± 2.35%, 15.27 ± 2.65%, 15.32 ± 2.40% vs. 15.97 ± 2.39%, p < 0.001). RDW level significantly increased with worsening Child-Pugh grade and BCLC stages. In addition, RDW level were negatively correlated with red blood cell (RBC) counts, hematocrit (HCT), lymphocyte (LY) counts, hemoglobin (Hb), blood platelet (PLT) counts, and positively correlated with aspartate-aminotransferase (AST), and total bile acid (TBA). ROC curve analysis showed that RDW level was 14.15% was the optimal prognostic cutoff point to determine the survival rate of HCC patients. In the univariate analysis followed by multivariate analysis, RDW level below 14.15% together with better Child-Pugh grade, better BCLC stages, and smaller tumor size were prognostic indicators for HCC patients. This indicated HCC patients with RDW level below 14.15% [hazard ratio of 0.530 (95% confidence interval, 0.395 - 0.710; p < 0.001)] had the lower mortality. CONCLUSIONS: RDW level was positively associated with tumor size. The prognosis was better for HCC patients with RDW levels below14.15% together with better Child-Pugh grade, better BCLC stages, and smaller tumor lesions. It suggested RDW level might be an easily obtainable and inexpensive prognostic indicator for HCC patients.

Anti-allergic function of α-Tocopherol is mediated by suppression of PI3K-PKB activity in mast cells in mouse model of allergic rhinitis.

BACKGROUND: Alpha-Tocopherol (α-TCP), one major form of vitamin E, has been known as a treatment for airway allergic inflammation. However, the role and mechanism of α-TCP in treating allergic rhinitis remains unclear. OBJECTIVE: In this study we examined the inhibitory function of α-TCP in a mouse model of allergic rhinitis. METHODS: Allergic phenotype was examined by hematoxylin and eosin staining. Total IgE, OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a levels were examined by ELISA. mRNA expression was measured by qPCR, protein levels were examined by Western Blot. RESULTS: Histological analysis of the nasal membranes revealed that there was a significant reduction in inflammatory cells appearance in cross-sections in alpha-TCP treatment of Ovalbumin (OVA)-sensitized mice compared to OVA sensitized animals. In addition, eosinophils were significantly reduced in nasal mucosa of alpha-TCP treatment of OVA-sensitized mice compared to the OVA group. Lower total IgE, OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a levels were found in alpha-TCP treatment of OVA-sensitized mice compared to the OVA group. Furthermore, we found that the subepithelial distribution of tryptase positive mast cells was reduced in the alpha-TCP treatment of OVA-sensitized mice. More importantly, the PI3K-PKB pathway was suppressed by α-TCP in mast cells. CONCLUSIONS: Our results demonstrated that α-TCP-mediated suppression of PI3K-PKB activity in mast cells is a potential mechanism of anti-allergic function of α-TCP.

Role of SCFAs in gut microbiome and glycolysis for colorectal cancer therapy.

Increased risk of colorectal cancer (CRC) is associated with altered intestinal microbiota as well as short-chain fatty acids (SCFAs) reduction of output The energy source of colon cells relies mainly on three SCFAs, namely butyrate (BT), propionate, and acetate, while CRC transformed cells rely mainly on aerobic glycolysis to provide energy. This review summarizes recent research results for dysregulated glucose metabolism of SCFAs, which could be initiated by gut microbiome of CRC. Moreover, the relationship between SCFA transporters and glycolysis, which may correlate with the initiation and progression of CRC, are also discussed. Additionally, this review explores the linkage of BT to transport of SCFAs expressions between normal and cancerous colonocyte cell growth for tumorigenesis inhibition in CRC. Furthermore, the link between gut microbiota and SCFAs in the metabolism of CRC, in addition, the proteins and genes related to SCFAs-mediated signaling pathways, coupled with their correlation with the initiation and progression of CRC are also discussed. Therefore, targeting the SCFA transporters to regulate lactate generation and export of BT, as well as applying SCFAs or gut microbiota and natural compounds for chemoprevention may be clinically useful for CRCs treatment. Future research should focus on the combination these therapeutic agents with metabolic inhibitors to effectively target the tumor SCFAs and regulate the bacterial ecology for activation of potent anticancer effect, which may provide more effective application prospect for CRC therapy.

Inhibition of glycolytic metabolism in glioblastoma cells by Pt3glc combinated with PI3K inhibitor via SIRT3-mediated mitochondrial and PI3K/Akt-MAPK pathway.

Glioblastoma multiforme (GBM) is the most malignant and aggressive glioma with abnormal expression of genes that mediate glycolytic metabolism and tumor cell growth. Petunidin-3-O-glucoside (Pt3glc) is a kind of anthocyanin in the red grape and derived beverages, representing the most common naturally occurring anthocyanins with a reduced incidence of cancer and heart diseases. In this study, whether Pt3glc could effectively regulate glycolysis to inhibit GBM cell was investigated by using the DBTRG-05MG cell lines. Notably, Pt3glc displayed potent antiproliferative activity and significantly changed the protein levels related to both glycolytic metabolism and GBM cell survival. The expression of the proapoptotic protein Bcl-2-associated X protein was increased with concomitant reduction on the levels of the antiapoptotic protein B-cell lymphoma 2 and caspase-3 activity. Furthermore, the levels of survival signaling proteins, such as protein kinase B (Akt) and phospho-Akt (Scr473), extracellular signal-regulated kinase (ERK) and phospho-ERK, were significantly decreased by Pt3glc in combination with the phosphoinositide 3-kinase (PI3K) inhibitor of LY294002. Most importantly, the levels of Sirtuin 3 (SIRT3) and phosphorylated p53 were also downregulated, indicating that Pt3glc combinated with PI3K inhibitor could induce GBM cell death may act via the SIRT3/p53-mediated mitochondrial and PI3K/Akt-ERK pathways. Our findings thus provide rational evidence that the combination of Pt3glc with PI3K inhibitor, which target alternative pathways in GBM cells, may be a useful adjuvant therapy in glioblastoma treatment.

Strategies to target energy metabolism in consensus molecular subtype 3 along with Kirsten rat sarcoma viral oncogene homolog mutations for colorectal cancer therapy.

Alterations in cellular energy metabolism play a critical role in colorectal cancer (CRC), which has been identified as the definition of consensus molecular subtypes (CMSs), and CMS3 tumors exhibit energy metabolism signatures along with Kirsten rat sarcoma viral oncogene homolog (KRAS)-activating mutations. This review summarizes the relationship between CMS3 tumors associated with mutated KRAS and energy metabolism in CRC, especially for the dysregulated energy metabolism that affects tumor cell proliferation, invasion, and migration. Furthermore, this review concentrates on the role of metabolic genes and factors and signaling pathways, which coupled with a primary energy source connected with the CMS3 associated with mutated KRAS, induce metabolic alterations. The strategies to target energy metabolism for the metabolic alterations in mutated KRAS CRC are also introduced. In conclusion, dysregulated energy metabolism has a close relationship with mutated KRAS in CMS3 tumors. Therefore, selective inhibitors or agents against metabolic targets or KRAS signaling may be clinically useful for CMS3 tumor treatment through a personalized approach for patients with cancer.

Strategies for targeting energy metabolism in Kirsten rat sarcoma viral oncogene homolog -mutant colorectal cancer.

Alterations in cellular energy metabolism play critical roles in colorectal cancer (CRC). These alterations, which correlate to KRAS mutations, have been identified as energy metabolism signatures. This review summarizes the relationship between colorectal tumors associated with mutated KRAS and energy metabolism, especially for the deregulated energy metabolism that affects tumor cell proliferation, invasion, and migration. Furthermore, this review will concentrate on the role of metabolic genes, factors and signaling pathways, which are coupled with the primary energy source connected with the KRAS mutation that induces metabolic alterations. Strategies for targeting energy metabolism in mutated KRAS CRC are also introduced. In conclusion, deregulated energy metabolism has a close relationship with KRAS mutations in colorectal tumors. Therefore, selective inhibitors, agents against metabolic targets or KRAS signaling, may be clinically useful for colorectal tumor treatment through a patient-personalized approach.

New strategies for targeting glucose metabolism-mediated acidosis for colorectal cancer therapy.

Colorectal cancer (CRC) is a heterogeneous group of diseases that are the result of abnormal glucose metabolism alterations with high lactate production by pyruvate to lactate conversion, which remodels acidosis and offers an evolutional advantage for tumor cells, even enhancing their aggressive phenotype. This review summarizes recent findings that involve multiple genes, molecules, and downstream signaling in the dysregulated glycolytic pathway, which can allow a tumor to initiate acid byproducts and to progress, thereby resulting in acidosis commonly found in the tumor microenvironment of CRC. Moreover, the relationship between CRC cells and the tumor acidic microenvironment, especially for regulating lactate production and lactate dehydrogenase A levels, is also discussed, as well as comprehensively defining different aspects of glycolytic pathways that affect cancer cell proliferation, invasion, and migration. Furthermore, this review concentrates on glucose metabolism-mediated transduction factors in CRC, which include acid-sensing ion channels, triosephosphate isomerase and key glycolysis-related enzymes that regulate glycolytic metabolites, coupled with the effect on tumor cell glycolysis as well as signaling pathways. In conclusion, glucose metabolism mediated by glycolytic pathways that are integral to tumor acidosis in CRC is demonstrated. Therefore, selective metabolic inhibitors or agents against these targets in glucose metabolism through glycolytic pathways may be clinically useful to regulate the tumor's acidic microenvironment for CRC treatment and to identify specific targets that regulate tumor acidosis through a cancer patient-personalized approach. Furthermore, strategies for modifying the metabolic processes that effectively inhibit cancer cell growth and tumor progression and activate potent anticancer effects may provide more effective antitumor prospects for CRC therapy.

A novel cardiovirus in wild rats.

BACKGROUND: Cardioviruses cause severe illnesses in rodents and humans. In recent years, novel cardioviruses have been frequently found, which promoted further studies of the genetic diversity of cardioviruses. Using viral metagenomics, we genetically characterized a novel cardiovirus (named SX1) from wild rat feces. The genomic structure of SX1 shared similar features with those of the Theiler's murine encephalomyelitis viruses, including a leader protein, four structural proteins and seven non-structural proteins. Phylogenetic analysis based on both structural proteins and non-structural proteins coding regions showed that SX1 was formed into a separate branch, being located between the branches of Theiler's murine encephalomyelitis viruses and Thera viruses. Variable resides presented in the Ser/Thr rich domain of L protein, VP1 loops, and VP2 puffs distinguished SX1 from Theiler's murine encephalomyelitis viruses, suggesting the different antigenicity and pathogenicity of SX1.

Full-length and defective enterovirus G genomes with distinct torovirus protease insertions are highly prevalent on a Chinese pig farm.

Recombination occurs frequently between enteroviruses (EVs) which are classified within the same species of the Picornaviridae family. Here, using viral metagenomics, the genomes of two recombinant EV-Gs (strains EVG 01/NC_CHI/2014 and EVG 02/NC_CHI/2014) found in the feces of pigs from a swine farm in China are described. The two strains are characterized by distinct insertion of a papain-like protease gene from toroviruses classified within the Coronaviridae family. According to recent reports the site of the torovirus protease insertion was located at the 2C/3A junction region in EVG 02/NC_CHI/2014. For the other variant EVG 01/NC_CHI/2014, the inserted protease sequence replaced the entire viral capsid protein region up to the VP1/2A junction. These two EV-G strains were highly prevalent in the same pig farm with all animals shedding the full-length genome (EVG 02/NC_CHI/2014) while 65% also shed the capsid deletion mutant (EVG 01/NC_CHI/2014). A helper-defective virus relationship between the two co-circulating EV-G recombinants is hypothesized.

Serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with CAD risk and lipid profiles in southern Chinese Han population.

BACKGROUND: Genetic and environment factors affect the occurrence and development of coronary artery disease (CAD). Proprotein convertase subtilisin/kexin type 9 (PCSK9), has been investigated extensively in the field of lipid metabolism and CAD. We performed this case-control study to investigate the relationship between serum PCSK9 levels and PCSK9 polymorphisms and lipid levels and CAD risk in a southern Chinese population. METHODS: A hospital-based case-control study with 1, 096 subjects, including 626 CAD patients and 470 controls, were conducted. Genotyping of PCSK9 polymorphisms was performed using polymerase chain reaction-ligase detection reaction (PCR-LDR) method. RESULTS: The frequencies of the AA, AG and GG genotypes of PCSK9 E670G polymorphism were 90.58, 9.27, and 0.16% in the CAD patients, compared with 88.72, 10.85 and 0.43% in the controls, respectively. No R46L variant was detected in this population. There were no significant differences in genotype and allele frequencies of PCSK9E670G polymorphism between the CAD group and the controls. Serum lipid levels were not significantly different in carriers with the G allele and those with the AA genotype. The median (QR) of PCSK9 concentration was 1205.00 ng/l (577.28-1694.13 ng/l) in cases and 565.87 ng/l (357.17-967.50 ng/l) in controls, respectively. Compared with controls, CAD patients had significantly higher PCSK9 levels (z = 4.559, P < 0.001). After adjusting for age, gender, essential hypertension, diabetic mellitus, smoking and lipid profiles, PCSK9 levels remain significantly associated with increased CAD susceptibility (OR = 1.002, 95% CI = 1.001-1.002, P < 0.001). The correlation analyses showed that serum PCSK9 levels were positively associated with triglyceride (TG), Apo B and atherogenic index of plasma (AIP) levels in controls. No significant association between the PCSK9 E670G polymorphism and serum PCSK9 levels was observed in the CAD group and the controls. CONCLUSIONS: The present study shows that serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with CAD risk in Southern Chinese Han population, and that serum PCSK9 levels are positively associated with AIP.

Strategies to Target Glucose Metabolism in Tumor Microenvironment on Cancer by Flavonoids.

The imbalance between glucose metabolism and cancer cell growth in tumor microenvironment (TME), which are closely related with the occurrence and progression of cancer. Accumulating evidence has demonstrated that flavonoids exert many biological properties, including antioxidant and anticarcinogenic activities. Recently, the roles and applications of flavonoids, particularly in relation to glucose metabolism in cancers, have been highlighted. Thus, the identification of flavonoids targeting alternative glucose metabolism pathways in TME may represent an attractive approach to the more effective therapeutic strategies for cancer. In this review, we will focus on the roles of flavonoids in regulating glucose metabolism and cancer cell growth in TME, such as proliferation advantage, cell mobility, and chemoresistance to cancer, as well as modifiers of thermal sensitivity. Not only have such large-scale endeavors been useful in providing fundamental insights into natural and synthesized flavonoids that can prevent and treat cancer, but also have led to the discovery of potential targets for cancer therapy.

The prognostic role of MAC30 in advanced gastric cancer patients receiving platinum-based chemotherapy.

AIM: We aimed to investigate a practical profile of MAC30 on chemotherapeutic response in gastric cancer (GC). PATIENTS & METHODS: We elected 87 GC patients receiving platinum-based chemotherapy in this study. MAC30 levels in tumor and adjuvant nontumor tissues were confirmed via reverse transcription-PCR to identify the clinical profile in GC and the correlation with therapeutic response. RESULTS: We found elevated MAC30 in GC compared with the matched adjacent nontumor tissues. GC with enhanced MAC30 exhibited poorer survival by Kaplan-Meier analysis and poor response to adjuvant platinum-based chemotherapy. A multivariate analysis showed that MAC30 was an independent prognostic factor of overall survival in GC receiving platinum-based chemotherapy. CONCLUSION: MAC30 could play as a potential biomarker for prognosis of GC with platinum-based chemotherapy.

A novel rodent Chapparvovirus in feces of wild rats.

Chapparvovirus, a recently determined new genus in the family Parvoviridae, can infect many species of animals including bats, chickens, and pigs. Here, using viral metagenomics method, we identified a novel Chapparvovirus from feces of wild rats and designated it as rat parvovirus 2 (RPV2). The nearly complete genome of RPV2 is 4222-nt long and includes two ORFs encoding a 654-aa nonstructural protein 1 (NS1) and a 472-aa capsid protein (VP), respectively. Phylogenetic analysis over the amino acid sequence of the NS1 showed that RPV2 clustered with Eidolon helvum parvovirus 2 (EHPV2), porcine parvovirus 7 (PPV7), and turkey parvovirus 1 (TP1), forming a separate clade. Sequence analysis indicated that the NS1 protein of RPV2 shared the highest amino acid sequence identity (51 %) with that of EHPV2. According to the genetic distance-based criteria, RPV2 identified here belongs to a novel species of Chapparvovirus.

Bufavirus Protoparvovirus in feces of wild rats in China.

Bufavirus (BuV) was first discovered from feces of children with acute diarrhea. It was subsequently detected from several animal species including shrews, bats, and nonhuman primates. In this study, we identified a novel Protoparvovirus, designated RatBuV, from the intestinal contents of wild rats using viral metagenomics. The near complete genome was 4643 nt encoding NS1, VP1, and VP2 proteins. Phylogenetic analysis over the complete genome showed that RatBuV clustered with Mpulungu BuV from shrews. Sequence analysis indicated that the putative protein sequences of NS1, VP1, and VP2 of RatBuV shared identities of 50.6-77.2, 48.3-77.3, and 47.1-78.3 %, respectively, with those of human BuVs, MpBuV, and WUHARV parvovirus, suggesting RatBuV belongs to a new species of Protoparvovirus. Our epidemiologic study indicated that the prevalence rate of RatBuV in the cohort of 40 wild rats is 12.5 % (5/40), which is higher than that of BuV in humans in a previous study.

A novel bocavirus from domestic mink, China.

Bocaviruses have been found in the feces of humans and a variety of animals, including pigs, cattle, dogs, gorillas, cats, and sea lions. Here, we have characterized the almost complete genome (5224 nt) of a novel bocavirus from feces of domestic minks, which has been provisionally named mink bocavirus. The NS1 protein of mink bocavirus shared 36.9-52 % amino acid sequence identities with those of other known bocaviruses and phylogenetically clustered with bocaviruses from other carnivores. According to the genetic distance-based criteria, mink bocavirus qualifies as a novel species of bocavirus. PCR of feces from a group of domestic minks, which included both healthy animals and animals suffering from diarrhea, revealed that 30 % (9/30) shed virus. However, no association between viral shedding and the presence of diarrhea could be determined.

MicroRNA-101 down-regulates sphingosine kinase 1 in colorectal cancer cells.

MicroRNAs (miRs) dysregulation is a general feature of colorectal cancer (CRC) and other solid tumors, and is associated cancer progression. In the current study, we demonstrate that microRNA-101 (miR-101) inhibits CRC cells probably through down-regulating sphingosine kinase 1 (SphK1). Our results showed that exogenously expressing miR-101 inhibited CRC cell (HT-29 and HCT-116 lines) growth in vitro. At the molecular level, miR-101 dramatically down-regulated SphK1 mRNA and protein expression, causing pro-apoptotic ceramide production in above CRC cells. On the other hand, inhibition of miR-101 through expressing antagomiR-101 increased SphK1 expression to down-regulate ceramide level in HT-29 cells. miR-101 expression increased the in vitro anti-CRC activity of conventional chemo-agents: paclitaxel and doxorubicin. CRC cells with SphK1-shRNA knockdown showed similar phenotypes as the miR-101-expressed CRC cells, presenting with elevated level of ceramide and high sensitivity to paclitaxel or doxorubicin. In vivo, HCT-116 xenograft growth in severe combined immuno-deficient (SCID) mice was dramatically inhibited by over-expressing miR-101. Further, miR-101 enhanced paclitaxel-induced anti-HCT-116 activity in vivo. Together, these results indicate that miR-101 exerts its anti-CRC activities probably through down-regulating SphK1.

Aberrant Protocadherin17 (PCDH17) Methylation in Serum is a Potential Predictor for Recurrence of Early-Stage Prostate Cancer Patients After Radical Prostatectomy.

BACKGROUND Prostate cancer is a one of the most common malignant diseases in men worldwide. Now it is a challenge to identify patients at higher risk for relapse and progression after surgery, and more novel prognostic biomarkers are needed. The aim of this study was to investigate the clinical significance of protocadherin17 (PCDH17) methylation in serum and its predictive value for biochemical recurrence (BCR) after radical prostatectomy. MATERIAL AND METHODS We evaluated the methylation status of PCDH17 in serum samples of 167 early-stage prostate cancer patients and 44 patients with benign prostatic hyperplasia (BPH) using methylation-specific PCR (MSP), and then evaluated the relationship between PCDH17 methylation and clinicopathologic features. Kaplan-Meier survival analysis and Cox analysis were used to evaluate its predictive value for BCR. RESULTS The ratio of PCDH17 methylation in prostate cancer patients was higher than in patients with BPH. Moreover, PCDH17 methylation was significantly associated with advanced pathological stage, higher Gleason score, higher preoperative PSA levels, and BCR. Kaplan-Meier survival analysis indicated that patients with methylated PCDH17 had shorter BCR-free survival time compared to patients with unmethylated PCDH17. Cox regression analysis indicated that PCDH17 methylation was an independent predictive factor for the BCR of patients after radical prostatectomy. CONCLUSIONS PCDH17 methylation in serum is a frequent event in early-stage prostate cancer, and it is an independent predictor of BCR after radical prostatectomy.

miR-125b inhibitor enhance the chemosensitivity of glioblastoma stem cells to temozolomide by targeting Bak1.

Temozolomide (TMZ) is a promising chemotherapeutic agent for treating glioblastomas. However, resistance develops quickly with a high frequency. Glioblastoma stem cells (GSCs) causing resistance to drug therapy were considered to be one of key factors. The mechanisms underlying GSCs resistance to TMZ are not fully understood. MicroRNAs (miRNAs) have emerged to play important roles in tumorigenesis and drug resistance. Previous study showed that miR-125b was necessary for GSCs fission and for making stem cells insensitive to chemotherapy. Thus, exploring the functions and mechanisms of miR-125b action on TMZ-treated GSCs would be valuable. In this study, we found that miR-125b was up-regulated in TMZ-resistant cells, inhibition of which caused a marked increase of TMZ-induced cytotoxicity and apoptosis and a subsequent decrease in the resistance to TMZ in GSCs. Moreover, we demonstrated that the pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) was a direct target of miR-125b. Down-regulation of Bak1 inhibited TMZ-induced apoptosis and led to an increased resistance to TMZ. Restoring Bak1 expression recovered TMZ sensitivity on GSCs. Taken together; our data strongly support an important role for miR-125b on conferring TMZ resistance through targeting Bak1 expression.