MUL1 identified as mitochondria-linked biomarker promoting cisplatin resistance in OC cells.

Ovarian cancer (OC) ranks among the prevalent tumors affecting the female reproductive system. The aim of this study was to evaluate mitochondria-associated platinum resistance genes using organoid models. Univariate Cox regression, LASSO and multivariate Cox regression analyses were performed on The Cancer Genome Atlas (TCGA) database to construct 2-gene prognostic signature (MUL1 and SSBP1), and GSE26712 dataset was used for external validation. In addition, the relationship between MUL1 and platinum resistance was examined by organoid culture, lentiviral transduction, CCK8 assay, and Western blot. The results showed that patients in the high-risk group exhibited significantly worse OS (P = 0.002, P = 0.017). Drug sensitivity analysis revealed that platinum resistance increased with the upregulation of MUL1 expression (Cor = 0.5154, P = 0.02). Our experimental findings demonstrated that knockout of the MUL1 gene significantly increased apoptosis and enhanced the sensitivity of the OC cell line A2780 to cisplatin. Through this study, we have provided strong evidence for further research on prognostic risk factors and individualized treatment in OC patients, and provided new insights into addressing platinum resistance in OC.

Pan-cancer analyses reveal genomics and clinical outcome association of the fatty acid oxidation regulators in cancer.

Background: Fatty acid oxidation (FAO) is considered to play a vital part in tumor metabolic reprogramming. But the comprehensive description of FAO dysregulation in tumors has not been unknown. Methods: We obtained FAO genes, RNA-seq data and clinical information from the Msigdb, TCGA and GTEx databases. We assessed their prognosis value using univariate cox analysis, survival analysis and Kaplan-Meier curve. We determined the function of FAO genes using gene set variation analysis. The correlation analysis was calculated by corrplot R package. Immunotherapy response was assessed through TIDE scores. The protein expression levels of FAO genes were validated using immunohistochemistry (IHC). Results: The FAO scores were highest in COAD but lowest in PCPG. FAO scores were significantly associated with the prognosis of some cancers in OS, DSS, DFI and PFI. Besides, gene set variation analysis identified that FAO scores were related to immune-related pathways, and immune infiltration analysis showed FAO scores were positively related to cancer-associated fibroblasts and various immune-related genes. TIDE scores were significantly decreased in ACC, CHOL, ESCA, GBM, LAML, SARC, SKCM and THCA compared with normal samples, while it was significantly increased in BLCA, LUAD, LUSC, PCPG, PRAD and STAD. Besides, most FAO genes were downregulated in pan-cancer compared with normal samples. Moreover, we found copy number variation (CNV) of FAO genes played a positive role in their mRNA expression, while methylation was negative. We determined FAO genes were closely related to some drugs in pan-cancer. Conclusions: FAO score is a novel and promising factor for predicting outcomes.

TRIM28 recruits E2F1 to regulate CBX8-mediated cell proliferation and tumor metastasis of ovarian cancer.

Chromobox protein homolog 8 (CBX8) is a transcriptional suppressor participated in various cancers. However, the function and mechanism of CBX8 in the progression of ovarian cancer (OC) are unclear. In this study, we found that CBX8 was upregulated in OC tissues originating from GEPIA and TNM databases, OC patients' samples from hospital, and OC cell lines. Furthermore, CBX8 knockdown by short hairpin RNA (shRNA) technology markedly inhibited proliferation and invasion, induced migration, cell cycle arrest, and apoptosis in vitro. Mechanistically, CBX8 activated PI3K/AKT/mTOR signaling pathway to take effect. In addition, TRIM28 and E2F1 were enriched in OC tissues from the TNM database and OC patients' samples similar to the results of CBX8. Correlation analysis indicated positive correlations among TRIM28, E2F1, and CBX8. E2F1 was proved to bind to the promoter regions of CBX8 and TRIM28, while TRIM28 recruited E2F1 to increase the expression of CBX8 to further increase cell viability, proliferation, and invasion, and decrease migration, apoptosis, and cell cycle progression. Finally, CBX8 or TRIM28 knockdown repressed tumor growth and metastasis of OC in vivo. Therefore, our study showed that the promoting effect of CBX8 on tumor growth and metastasis of OC was participated in the PI3K/AKT/mTOR signaling, TRIM28 and E2F1. Our findings suggested that CBX8 could serve as a potential marker and therapeutic target for OC patients.

Identifying Immune Cell Infiltration and Hub Genes Related to M2 Macrophages in Endometriosis by Bioinformatics Analysis.

Endometriosis (EM) is a chronic, estrogen-dependent inflammatory disease. Presently, the pathophysiology of EM is still unclear, and numerous studies have established that the immune system plays a major role in the pathophysiology of EM. Six microarray datasets were downloaded from the GEO public database. A total of 151 endometrial samples (72 ectopic endometria and 79 controls) were included in this study. CIBERSORT and ssGSEA were applied to calculate the immune infiltration of EM and control samples. Moreover, we validated four different correlation analyses to explore immune microenvironment of EM and finally identified M2 macrophage-related hub genes and further conducted the specific immunologic signaling pathway analysis by GSEA. The logistic regression model was investigated by ROC and further validated by two external datasets. From the results of the two immune infiltration assays, we concluded that M2 macrophages, regulatory T cells (Tregs), M1 macrophages, activated B cells, T follicular helper cells, activated dendritic cells, and resting NK cells have a significant difference between control and EM tissues. Through multidimensional correlation analysis, we found that macrophages play an important central role in cell-to-cell interactions, especially M2 macrophages. Four immune-related hub genes, namely FN1, CCL2, ESR1, and OCLN, are closely related to M2 macrophages and play a crucial role in the occurrence and immune microenvironment of endometriosis. The combined AUC of ROC prediction model in test and validation sets were 0.9815 and 0.8206, respectively. We conclude that M2 macrophages play a central role in the immune-infiltrating microenvironment of EM.

Identification and validation of shared genes and key pathways in endometriosis and endometriosis-associated ovarian cancer by weighted gene co-expression network analysis and machine learning algorithms.

BACKGROUND: Epidemiological studies reported that patients with endometriosis had an increased risk of developing endometriosis-associated ovarian cancer (EAOC). The present study aimed to identify shared genes and key pathways that commonly interacted between EAOC and endometriosis. METHODS: The expression matrix of ovarian cancer and endometriosis were collected from the Gene Expression Omnibus database. The weighted gene co-expression network analysis (WGCNA) was used to construct co-expression gene network. Machine learning algorithms were applied to identify characteristic genes. CIBERSORT deconvolution algorithm was used to explore the difference in tumor immune microenvironment. Furthermore, diagnostic nomogram was constructed and evaluated for supporting clinical practicality. RESULTS: We identified 262 shared genes between EAOC and endometriosis via WGCNA analysis. They were mainly enriched in cytokine-cytokine receptor interaction. After protein-protein interaction network and machine learning algorithms, we recognized two characteristic genes (EDNRA, OCLN) and established a nomogram that presented an outstanding predictive performance. The hub genes demonstrated remarkable associations with immunological functions. Survival analysis indicated that dysregulated expressions of EDNRA and OCLN were closely correlated with prognosis of ovarian cancer patients. gene set enrichment analyses revealed that the two characteristic genes were mainly enriched in the cancer- and immune-related pathways. CONCLUSION: Our findings pave the way for further investigation of potential candidate genes and will aid in improving the diagnosis and treatment of EAOC in endometriosis patients. More research is required to determine the exact mechanisms by which these two hub genes affecting the development and progression of EAOC from endometriosis.

Nonpoint Source Pollution (NPSP) Induces Structural and Functional Variation in the Fungal Community of Sediments in the Jialing River, China.

Nonpoint source pollution (NPSP) from human production and life activities causes severe destruction in river basin environments. In this study, three types of sediment samples (A, NPSP tributary samples; B, non-NPSP mainstream samples; C, NPSP mainstream samples) were collected at the estuary of the NPSP tributaries of the Jialing River. High-throughput sequencing of the fungal-specific internal transcribed spacer (ITS) gene region was used to identify fungal taxa. The impact of NPSP on the aquatic environment of the Jialing River was revealed by analysing the community structure, community diversity, and functions of sediment fungi. The results showed that the dominant phylum of sediment fungi was Rozellomycota, followed by Ascomycota and Basidiomycota (relative abundance > 5%). NPSP caused a significant increase in the relative abundances of Exosporium, Phialosimplex, Candida, Inocybe, Tausonia, and Slooffia, and caused a significant decrease in the relative abundances of Cercospora, Cladosporium, Dokmaia, Setophaeosphaeria, Paraphoma, Neosetophoma, Periconia, Plectosphaerella, Claviceps, Botrytis, and Papiliotrema. These fungal communities therefore have a certain indicator role. In addition, NPSP caused significant changes in the physicochemical properties of Jialing River sediments, such as pH and available nitrogen (AN), which significantly increased the species richness of fungi and caused significant changes in the fungal community ß-diversity (P < 0.05). pH, total phosphorus (TP), and AN were the main environmental factors affecting fungal communities in sediments of Jialing River. The functions of sediment fungi mainly involved three types of nutrient metabolism (symbiotrophic, pathotrophic, and saprotrophic) and 75 metabolic circulation pathways. NPSP significantly improved the pentose phosphate pathway, pentose phosphate pathway, and fatty acid beta-oxidation V metabolic circulation pathway functions (P < 0.05) and inhibited the chitin degradation to ethanol, super pathway of heme biosynthesis from glycine, and adenine and adenosine salvage III metabolic circulation pathway functions (P < 0.05). Hence, NPSP causes changes in the community structure and functions of sediment fungi in Jialing River and has adversely affected for the stability of the Jialing River Basin ecosystem.

A novel CDKN1A-JAZF1 gene fusion in low-grade endometrial stromal sarcoma arising from endometriosis in abdominal wall cesarean section scar: A case report and literature review.

OBJECTIVE: We report a low-grade endometrial stromal sarcoma (ESS) with a novel CDKN1A-JAZF1 fusion gene arising from abdominal wall endometrioma. CASE REPORT: A 40-year-old woman presented with a 5.5-cm abdominal wall mass juxtaposed to the postoperative scar of two cesarean sections. Histologically, the tumor exhibited obvious tongue-like protrusions into the surrounding tissue, showed spindle cells with multinodular growth pattern that occasionally rotate around small arteries. Immunohistochemically, the tumor cells were positive for CD10, estrogen receptor (ER), progesterone receptor (PR), negatively stained for smooth muscle actin (SMA), CD117, CyclinD1. In addition, a previously undescribed gene fusion between CDNK1A 5' end of exon 1(NM_000389.5) and JAZF1 3' end of exon 5 (NM_175,061,3) was reported in this case. CONCLUSION: This report of ESS suggesting that rapidly growing abdominal wall masses without menstruation-related should be promptly evaluated and treated aggressively. In addition, we have expanded the molecular landscape of low-grade ESS.

The impact of river sand mining on remobilization of lead and cadmium in sediments - A case study of the Jialing River.

Due to the fast pace of urbanization worldwide, industrial sand mining activities have imposed great pressure on the environment, and consequently, these activities have led to serious environmental problems in aquatic ecosystems. However, the current understanding of the effect of sand mining on heavy metal remobilization in river sediments remains incomplete. The present study employed sediment quality guidelines (SQGs) and the sequential extraction (SE) and diffusive gradients in thin films (DGT) techniques to comprehensively investigate the effect of sand mining on the remobilization process of heavy metals in the aquatic system of the Jialing River. The SQGs results indicated that stations (S1 to S4) with sand mining disturbance exhibited Pb and Cd accumulation in surface sediments. Both Ctotal-Pb (61.78-122.04 mg·kg-1) and Ctotal-Cd (0.85-3.96 mg·kg-1) were higher than CSQGI (60 mg·kg-1 for Pb and 0.5 mg·kg-1 for Cd) and TEC (35.8 mg·kg-1 for Pb and 0.99 mg·kg-1 for Cd) limitation in most of sand mining stations. Pb and Cd were mainly bounded in the acid-soluble/exchangeable fraction (F1) and oxidizable fraction (F3) of the surface sediments. At the four stations with sand mining disturbance, about 5-10 folds of DGT-labile Pb and Cd were released in deep sediments (-9 to -12 cm), and Pb and Cd exhibited a transport trend from the sediments into the overlying water, while the above phenomenon was not observed at the two stations without sand mining activities. Correlation analysis revealed that DGT-labile Pb and Cd were suitably correlated with the F1 and F3 fractions, indicating that the acid-soluble/exchangeable and oxidizable fractions were the main sources leading to Pb and Cd remobilization in the sediments. A potential mechanism explanation may be that (1) intense sediment stirring could result in remobilization of the weakly bound fraction, which is related to the contribution of the F1 fraction, and (2) Cd/Pb experienced a corelease process with sulfur due to O2 introduction (elevation of the dissolved oxygen level) attributed to sediment evacuation, which is related to the contribution of the F3 fraction. The above results suggested that sand mining in the Jialing River should be paid high attention to prevent heavy metal pollution in aquatic ecosystem.

Is there different prognosis between cervical endometrioid adenocarcinoma and ordinary cervical adenocarcinoma in a propensity score matching study based on the surveillance, epidemiology, and end results (SEER) database?

Background: There has been lack of guidance for stratify treatment between cervical endometrioid adenocarcinoma (EC) and ordinary cervical adenocarcinoma (AC), therefore understanding the difference of prognosis between EC and AC is important for individualized therapy for these patients. Methods: In this study, we compare the survival outcomes between cervical EC and AC patients from the SEER database. we analyzed 2,554 patients for overall survival (OS) and 2,527 patients for disease-specific survival (DSS), Cox regression and Kaplan-Meier analyses were conducted to analyze the survival outcomes of the AC and EC patients, a 1:1 propensity score matching (PSM) method was used to match patients and balance various factors, OS and DSS were analyzed among the subgroups before and after 1:1 PSM. Results: In the unmatched cohort, in the multivariate analysis, no statistically significant difference was found in terms of OS (P=0.24) and DSS (P=0.20) between the EC and AC patients, The 3- and 5-year OS rates were 77.89% and 72.65% for the AC patients, and 83.38% and 75.64% for the EC patients respectively. The 3- and 5-year DSS rates were 84.93% and 79.69% for the EC patients, 83.97% and 76.78% for the AC patients, respectively. In the PSM cohort, 280 AC patients and 280 EC patients were included in the analysis of OS. 273 AC patients and 275 EC patients were included in the analysis of DSS, the Kaplan-Meier analysis and the multivariate analysis also produced similar results for the unmatched groups. Conclusions: There were no statistically significant differences in OS and DSS between the cervical EC and AC patients.

Identification of Tumor Microenvironment and DNA Methylation-Related Prognostic Signature for Predicting Clinical Outcomes and Therapeutic Responses in Cervical Cancer.

Background: Tumor microenvironment (TME) has been reported to have a strong association with tumor progression and therapeutic outcome, and epigenetic modifications such as DNA methylation can affect TMB and play an indispensable role in tumorigenesis. However, the potential mechanisms of TME and DNA methylation remain unclear in cervical cancer (CC). Methods: The immune and stromal scores of TME were generated by the ESTIMATE algorithm for CC patients in The Cancer Genome Atlas (TCGA) database. The TME and DNA methylation-related genes were identified by the integrative analysis of DNA promoter methylation and gene expression. The least absolute shrinkage and selection operator (LASSO) Cox regression was performed 1,000 times to further identify a nine-gene TME and DNA methylation-related prognostic signature. The signature was further validated in Gene Expression Omnibus (GEO) dataset. Then, the identified signature was integrated with the Federation International of Gynecology and Obstetrics (FIGO) stage to establish a composite prognostic nomogram. Results: CC patients with high immunity levels have better survival than those with low immunity levels. Both in the training and validation datasets, the risk score of the signature was an independent prognosis factor. The composite nomogram showed higher accuracy of prognosis and greater net benefits than the FIGO stage and the signature. The high-risk group had a significantly higher fraction of genome altered than the low-risk group. Eleven genes were significantly different in mutation frequencies between the high- and low-risk groups. Interestingly, patients with mutant TTN had better overall survival (OS) than those with wild type. Patients in the low-risk group had significantly higher tumor mutational burden (TMB) than those in the high-risk group. Taken together, the results of TMB, immunophenoscore (IPS), and tumor immune dysfunction and exclusion (TIDE) score suggested that patients in the low-risk group may have greater immunotherapy benefits. Finally, four drugs (panobinostat, lenvatinib, everolimus, and temsirolimus) were found to have potential therapeutic implications for patients with a high-risk score. Conclusions: Our findings highlight that the TME and DNA methylation-related prognostic signature can accurately predict the prognosis of CC and may be important for stratified management of patients and precision targeted therapy.

MiR-486-5p Act as a Biomarker in Endometrial Carcinoma: Promotes Cell Proliferation, Migration, Invasion by Targeting MARK1.

BACKGROUND: miRNA expression acts as a potential biomarker in many diseases including endometrial carcinoma (EC). miR-486-5p dysregulation is observed in several tumor types, but the roles of miR-486-5p in EC are hardly ever studied. OBJECTIVE: This study aimed to analyze the expression profile of miR-486-5p in tumor tissues and serum samples of patients with EC and explore the target prediction, function analysis and validation in immortal cell lines. PATIENTS AND METHODS: A total of 42 freshly paired EC tissues, the corresponding adjacent non-neoplastic tissues and serum samples were also collected from patients with EC, and 42 matched normal serum samples were included as control group. The level of miR-486-5p expression was tested by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was determined by colony formation assay and CCK-8 assay. Furthermore, functional evaluation of miR-486-5p on migration was performed by wound-healing assay and invasion was estimated by transwell invasion assay. qRT-PCR, luciferase reporter assay and Western blotting (WB) were performed to verify the targeting of MARK1 by miR-486-5p. RESULTS: miR-486-5p was significantly up-regulated in EC tissues and serum samples, promoting the proliferation, migration and invasive activities of EC cells by targeting MARK1. CONCLUSION: These data indicated miR-486-5p as a novel molecular biomarker for diagnosing and treating EC, and MARK1 might act as a critical and functional target of miR-486-5p with the implications on cell proliferation, migration and invasiveness of EC tumor cells.

Combination of Preoperative D-Dimer and Platelet Distribution width Predicts Postoperative Deep Venous Thrombosis in Patients with Cervical Carcinoma

Background: Deep venous thrombosis (DVT) is associated with severe morbidity and mortality in cancer. Platelet distribution width (PDW), a platelet index, indicates variation in platelet size. We aimed to investigate whether the combination of D-dimer and PDW could have a better performance in predicting DVT in patients with cervical carcinoma. Materials and Methods: In 198 consecutive cervical carcinoma patients without preoperative DVT, preoperative D-dimer and PDW levels were measured. Compression ultrasonography was performed in all cervical carcinoma patients before surgery, as well as one month, three months, six months, and 12 months. Results: During a median period of 12 months, 17 of the 198 patients (8.6 %) developed DVT. PDW levels were reduced and D-dimer levels were increased in patients with DVT events compared to those without DVT. Multivariate Cox analysis revealed that both PDW and D-dimer were independent predictors for DVT events. The area under the ROC curve was 0.628 (95% CI: 0.556 to 0.695, p=0.142) when D-dimer was used alone, whereas it increased to 0.777 (95% CI: 0.712 to 0.833, p<0.011) with the addition of PDW. Incorporation of PDW into the D-dimer model significantly improved the predictive value. Conclusions: The combination of preoperative D-dimer and PDW improves the predictive power of postoperative DVT risk in patients with cervical carcinoma.

A water-soluble polysaccharide from the roots of Polygala tenuifolia suppresses ovarian tumor growth and angiogenesis in vivo.

PTP, one polysaccharide extracted from the roots of Polygala tenuifolia, has displayed anti-cancer activity in several types of ovarian cancer cells. This study aims to elucidate the structure of PTP and investigate its anticancer effects against SKOV3 xenograft tumor growth in BALB/c mice, as well as the underlying mechanisms involved. GC-MS and NMR data indicate that PTP has a backbone composed of 1,4,6-linked-ß-Galp, 1,4-linked-ß-Galp and 1,4-linked-ß-Glcp, with non-reducing terminal 1-linked-α-Glcp attached to O-6 of 1,4,6-linked-ß-Galp. The tumor growth was suppressed in mice following two week's PTP administration (10, 20 and 40mg/kg) due to the induction of apoptosis, as detected by TUNEL assay. Moreover, lower serum VEGF and EGFR levels were observed in BALB/c mice treated with different doses of PTP when compared with that in untreated mice. Also, EGFR, VEGF, and CD34 were decreased in both transcript and protein levels in the tumor-bearing mice upon PTP treatment. Taken together, our data suggest that PTP appears to be a powerful chemopreventive agent for the patients with ovarian cancer, especially at advanced stage.

Effects of CD44 and E-cadherin overexpression on the proliferation, adhesion and invasion of ovarian cancer cells.

CD44 is a prognostic indicator of shorter survival time in ovarian cancer. E-cadherin fragmentation promotes the progression of ovarian cancer. However, the effects of CD44 and E-cadherin overexpression on ovarian cancer cells have remained elusive. The present study aimed to investigate the effects of overexpression of CD44 and E-cadherin on cell proliferation, adhesion and invasion of SKOV-3 and OVCAR-3 ovarian cancer cells. Overexpression of CD44 and E-cadherin was achieved by transfecting SKOV-3 and OVCAR-3 cells with viruses carrying the CD44 or E-cadherin gene, respectively. Expression of CD44 and E-cadherin was detected by western blot analysis. The proliferation of SKOV-3 and OVCAR-3 cells was measured by a Cell Counting Kit-8 at 0, 24 and 48 h after viral transfection. The adhesion ability of SKOV-3 and OVCAR-3 cells to the endothelial layer was detected. A Transwell invasion assay was utilized to assess the invasion ability of the cells. Overexpression of CD44 and E-cadherin in SKOV-3 and OVCAR-3 cells was confirmed by western blot. Compared with the blank or negative control groups, the CD44 overexpression groups of SKOV-3 and OVCAR-3 cells exhibited an increased cell proliferation rate at 24 and 48 h, whereas overexpression of E-cadherin did not alter the proliferation of these cells. Furthermore, compared with the blank and negative control groups, the cell adhesion and invasion ability in the CD44 overexpression groups of SKOV-3 and OVCAR-3 cells was markedly higher. There were no significant differences in adhesion ability between the E-cadherin overexpression group and the blank/negative control group. Of note, overexpression of E-cadherin decreased the invasive ability of SKOV-3 and OVCAR-3 cells. In conclusion, Overexpression of CD44 increased the proliferation, adhesion and invasion of ovarian cancer cells, while overexpression of E-cadherin decreased the invasion of ovarian cancer cells.

EphA3 promotes malignant transformation of colorectal epithelial cells by upregulating oncogenic pathways.

Ephrin Type-A Receptor 3 (EphA3) belongs to the ephrin receptor subfamily of the protein tyrosine kinase family, and plays an important role in embryogenesis and neurogenesis. This study aimed to investigate the role of EphA3 in promoting malignant transformation of colorectal epithelial cells, and explore underlying molecular mechanisms. Colorectal cancer tissue specimens from 68 patients were analyzed for EphA3 expression. EphA3 expression levels were manipulated in rat colon epithelial cell lines. We found that EphA3 expression level in tumor tissues was associated with patient age (P = 0.015), tumor differentiation (P = 0.001), and lymph node metastasis (P = 0.039). Overexpression of EphA3 and its constitutively active mutants promoted colony formation, migration and invasion, and tumorigenicity of colon epithelial cells in nude mice. The cDNA and lncRNA microarray profiling data revealed that differentially expressed genes and lncRNAs in EphA3 or mutant-transfected cells were associated with cell proliferation, invasion and angiogenesis. Our findings reveal the mechanisms underlying the oncogenic activities of EphA3 in colorectal cells, which could provide novel targets for the prevention, early diagnosis, and treatment of colorectal cancer.

EphB6 overexpression and Apc mutation together promote colorectal cancer.

The erythropoietin-producing hepatocyte (Eph) family tyrosine kinases play important roles in tumorigenesis and cancer aggression. In this study, we investigated the role of EphB6 in oncogenic transformation of colorectal epithelial cells in vitro and in vivo. EphB6 is upregulated in human colorectal cancer (CRC) tissues as compared to normal tissues, and its overexpression promotes proliferation, migration and invasion by IMCE colorectal adenoma cells, in which one Apc allele is mutated. EphB6 overexpression together with Apc mutation leads to the development of colorectal tumors in vivo. Expression microarrays using mRNAs and lncRNAs isolated from EphB6-overexpresssing IMCE and control cells revealed a large number of dysregulated genes involved in cancer-related functions and pathways. The present study is the first to demonstrate that EphB6 overexpression together with Apc gene mutations may enhance proliferation, invasion and metastasis by colorectal epithelial cells. Microarray data and pathway analysis of differentially expressed genes provided insight into possible EphB6-regulated mechanisms promoting tumorigenesis and cancer progression. EphB6 overexpression may represent a novel, effective biomarker predictive of cell proliferation, invasion and metastasis patterns in CRC tumors.

Knockdown of protein phosphatase 5 inhibits ovarian cancer growth in vitro.

Ovarian cancer is the most common cause of gynecological cancer-related mortality. Serine/threonine protein phosphatase 5 (PP5, PPP5C) has been recognized to be involved in the regulation of multiple cellular signaling cascades that control diverse cellular processes, including cell growth, differentiation, proliferation, motility and apoptosis. In this study, to evaluate the functional role of PP5 in ovarian cancer cells, lentivirus-mediated RNA interference (RNAi) was applied to silence PPP5C in the human ovarian cancer cell line CAOV-3. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell colony forming ability was measured by colony formation. Cell cycle progression was determined by propidium iodide staining and flow cytometry. The results demonstrated that lentivirus-mediated RNAi specifically suppressed the expression of PPP5C at the mRNA and protein levels in CAOV-3 cells. Further investigations revealed that PP5 knockdown significantly inhibited the proliferation and colony formation of CAOV-3 cells. Moreover, the cell cycle of CAOV-3 cells was arrested at the G0/G1 phase following PP5 knockdown. This study highlights the crucial role of PP5 in promoting ovarian cancer cell proliferation, and provides a foundation for further study into the clinical potential of lentiviral-mediated delivery of PP5 RNAi therapy for the treatment of ovarian cancer.

Polygala tenuifolia polysaccharide PTP induced apoptosis in ovarian cancer cells via a mitochondrial pathway.

One purified polysaccharide protein tyrosine phosphatase (PTP) was isolated from the roots of Polygala tenuifolia. The aim of the present study is to investigate the antitumor effect of PTP on human ovarian cancer OVCAR-3 cells and explore the molecular mechanism of the action involved. The results of MTT assay and apoptosis detection assay showed that PTP inhibited cellular proliferation of OVCAR-3 cells and induced apoptotic cellular death via arresting cell circle at the G0/G1 phase. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis identified that bcl-2 gradually decreased at both transcription and protein levels after PTP treatment for 48 h in OVCAR-3 cells, while those of bax, cytochrome c, caspase-3, and caspase-9 increased. In addition, the low expression of NF-κB in PTP-treated OVCAR-3 cells would trigger the extrinsic pathway of programmed cell death signaling in tumor cells. These results together suggest that PTP may induce apoptosis of OVCAR-3 cells through a mitochondrial pathway.

Polygala tenuifolia polysaccharide (PTP) inhibits cell proliferation by repressing Bmi-1 expression and downregulating telomerase activity.

In our previous study, we isolated a homogeneous polysaccharide (PTP) with antitumor activity from the roots of Polygala tenuifolia. In view of the close correlation between Bmi-1 expression and progression of ovarian cancer, we intend to elucidate the mechanism of its activity by determining the Bmi-1 expression and the telomerase activity in human ovarian carcinoma OVCAR-3 cells following treatment with PTP at three concentrations of 0.5, 1, and 2 mg/mL for 48 h. MTT and colony-forming assays revealed that PTP had a significant inhibitory effect on the cell growth and colony formation of OVCAR-3 cells. Furthermore, Western blot and real-time PCR analysis showed that PTP inhibited Bmi-1 both in protein and transcript levels. Besides, the telomerase activity in OVCAR-3 cells was also downregulated after PTP treatment for 48 h. Taken together, the inhibitory effect of PTP on the cell growth was at least in part mediated via the downregulation of Bmi-1 expression and the telomerase activity in OVCAR-3 cells, and PTP might be a new candidate for chemotherapeutic agent against human ovarian cancer.

Elevated expression of hyaluronic acid binding protein 1 (HABP1)/P32/C1QBP is a novel indicator for lymph node and peritoneal metastasis of epithelial ovarian cancer patients.

The present study aims to clarify whether hyaluronan binding protein 1 (HABP1/p32/C1QBP) is an indicator of peritoneal and lymph node metastasis in epithelial ovarian cancer (EOC), which to the authors' knowledge is not previously reported by others. Western blot analysis demonstrated that HABP1 was highly overexpressed in most metastatic lesions. Of 89 patients whose primary tumors showed high HABP1 expression on immunohistochemical staining, 85 (95.5%) presented peritoneal metastases and 43 (48.3%) had lymph node metastases. Univariate and multivariate logistic regression analyses revealed that HABP1 overexpression correlated with peritoneal dissemination and lymph node metastasis in EOC. The specificity and positive predictive value of HABP1 staining were shown to be better for peritoneal metastasis, while the negative and sensitivity predictive value of HABP1 staining were better for lymph node metastasis. The odds ratio of high versus low staining for peritoneal spread was 9.236 (95% confidence interval (CI), 2.705, 19.316), and that for lymph node metastasis was 8.614 (95% CI, 2.507, 21.039). Furthermore, HABP1 protein may potentially be used alone or in combination with other markers as a predictive marker of EOC patients with lymph node metastasis and/or peritoneal dissemination.