The effects of laparoscopic and laparotomy extensive hysterectomy on the safety of ureterovaginal fistula infection in patients with cervical cancer.

This study aimed to investigate the effect of laparoscopic and laparotomy extensive hysterectomy on the safety of ureterovaginal fistula infection in patients with cervical cancer. For this purpose, a total of 90 patients with early cervical cancer admitted to Affiliated Huaian No.1 People's Hospital of Nanjing Medical University from February 2021 to May 2022 were randomly divided into laparoscopy group and laparotomy group, with 45 cases in each group. The laparoscopy group was treated with laparoscopic extensive hysterectomy, while the laparotomy group was treated with laparotomy extensive hysterectomy. The KPS score, adverse reactions, as well as serum creatinine and urea nitrogen were compared between the two groups. Results showed that after surgery, the KPS score in both groups was higher than before treatment, and the KPS score in laparoscopy group was higher than that in laparotomy group, the difference was statistically significant (P<0.05). After operation, the incidence of adverse reactions in laparotomy group was higher than that in the laparoscopy group, the difference was statistically significant (P<0.05). Moreover, after operation, the levels of creatinine and urea nitrogen in laparoscopy group were significantly lower than those in laparotomy group, the differences were statistically significant (P<0.05). In conclusion, both laparoscopic and laparotomy extensive hysterectomy may lead to ureterovaginal fistula infection in patients with cervical cancer. However, compared with laparotomy extensive hysterectomy, laparoscopic extensive hysterectomy had higher safety and significantly improved the quality of life of patients, which was worthy of popularization and application in clinical practice.

A new isopimarane-type diterpene with anti-inflammatory activity from the Clinacanthus nutans.

A new isopimarane-type diterpene clinacanoid A (1) together with seven known terpenoids (2-8) were obtained from the Clinacanthus nutans. Their structures were elucidated based on extensive spectroscopic analysis (NMR, HR-ESI-MS), and the absolute configuration of 1 was established based on single crystal X-ray diffraction. The inhibitory activity of all the compounds on NO production in lipopolysaccharide-induced (LPS) mouse leukemic monocyte macrophage RAW264.7 cells was evaluated. Among them, compounds 1 and 3 showed potential anti-inflammatory activities, with IC50 values of 13.3 ± 0.3 and 12.4 ± 0.4 µM, respectively.

[Retracted] MicroRNA­362 is downregulated in cervical cancer and inhibits cell proliferation, migration and invasion by directly targeting SIX1.

Following the publication of the above article, a concerned reader drew to the Editor's attention that the Transwell cell migration and invasion assay data featured in Fig. 2C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Oncology Reports, or were under consideration for publication at around the same time (some of which have been retracted). Furthermore, a number of overlapping data panels were identified comparing the migration and invasion assay data in Figs. 5C and 6C, such that data which were intended to show the results from differently performed experiments appeared to have been derived from the same original source(s). In view of the fact that certain of these data had already apparently been published previously, and given the lack of rigour on the part of the authors in assembling the data in Figs. 5 and 6, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 37: 501­509, 2017; DOI: 10.3892/or.2016.5242].

Comparison of clinical outcomes among patients with isolated axial vs muscular calf vein thrombosis: A systematic review and meta-analysis.

OBJECTIVE: Thrombi in the axial calf veins have quite different anatomical and physiological characteristics from that in the muscular calf veins, but their treatment was usually addressed in the same manner. We performed a meta-analysis of randomized and cohort studies to compare clinical outcomes among patients with isolated axial vs muscular calf deep vein thrombosis (DVT). METHODS: Recurrent venous thromboembolism (VTE) was selected as the primary outcome. Resolution, proximal propagation of calf DVT, pulmonary embolism (PE), major bleeds, and clinically relevant non-major bleeds were separately analyzed as secondary outcomes. Data were pooled and compared with risk ratio (RR) and 95% confidence interval (CI). RESULTS: Thirteen studies, consisting of 4889 patients, met the inclusion criteria and were included for analysis. A greater rate of recurrent VTE (FE model: RR, 1.23; 95% CI, 1.00-1.53; I2 = 29%), resolution (FE model: RR, 1.32; 95% CI, 1.01-1.72; I2 = 31%), proximal propagation (FE model: RR, 1.63; 95% CI, 1.10-2.41; I2 = 40%), and PE (FE model: RR, 2.79; 95% CI, 1.31-5.95; I2 = 0%) in the axial group compared with the muscular group. There was no difference in the pooled estimates for major bleeds (FE model: RR, 1.09; 95% CI, 0.61-1.95; I2 = 0%), and clinically relevant non-major bleeds (FE model: RR, 1.80; 95% CI, 0.93-3.48) in the axial and muscular arms. CONCLUSIONS: Patients with calf DVT limited to muscular veins might have a lower rate of recurrent VTE, resolution, proximal propagation, and PE vs those with axial calf vein involvement and exhibited similar safety outcomes.

Identification and validation of M2 macrophage-related genes in endometriosis.

Aims: M2 macrophage is believed to play an important role in the development of endometriosis. This study aimed to identify several key genes related to the M2 macrophage in endometriosis. Method: Differential expressed genes between endometriosis and non-endometriosis were identified based on three microarray datasets from the Gene Expression Omnibus database. Gene modules significantly associated with M2 macrophage were identified from the weighted gene co-expression network analysis. Furthermore, by intersecting the differential expressed genes and M2 macrophage-associated module genes, M2 macrophage-related genes in endometriosis were identified. Functional analyses of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes for these genes were then performed. Following, the least absolute shrinkage and selection operator, random forest, and receiver operating characteristic curves were further conducted to identify the key M2 macrophage-related genes in endometriosis. Finally, the expressions of key genes in endometriosis, as well as their correlations with M2 macrophages were verified in an independent validation cohort. Results: Totally, 185 M2 macrophage-related genes were identified, and they were mainly enriched in functions associated with the cell cycle, oocyte maturation, and immune response. Following machine learning algorithms, eight key genes were selected in the endometriosis: PGR, OLFM4, PIP5K1B, CCNA1, BRIP1, CADM1, PRAME, and GCNT1. The eight key genes were confirmed to be negative with M2 macrophage infiltration levels. Furthermore, the expression levels of these genes were significantly lower in the middle secretory stage while relevantly higher in the proliferative stage. The validation analysis also showed similar outcomes with the above results. Conclusion: Eight M2 macrophage-related genes were identified as potential biomarkers of endometriosis, providing novel understanding of immune cells in the endometriosis.

Influence of lymphadenectomy on survival and recurrence in patients with early-stage epithelial ovarian cancer: a meta-analysis.

BACKGROUND: This meta-analysis aimed to evaluate the effectiveness of lymphadenectomy on survival and recurrence in patients with early-stage epithelial ovarian cancer (eEOC). METHODS: Relevant studies were searched from four online databases. Hazard ratios (HRs) with 95% confidence intervals (CIs) or risk ratios (RRs) with 95% CIs were used to evaluate the effects of lymphadenectomy on overall survival (OS), progression-free survival (PFS), and recurrence rates. A subgroup analysis was performed to explore the sources of heterogeneity, followed by sensitivity and publication bias assessments. RESULTS: Fourteen articles involving 22,178 subjects were included. Meta-analysis revealed that lymphadenectomy was significantly associated with improved OS (HR = 0.72; 95% CI:0.61, 0.84; P < 0.001), improved PFS (HR = 0.74; 95% CI: 0.67, 0.80; P < 0.001), and reduced recurrence rates (RR = 0.72; 95% CI: 0.60, 0.85; P < 0.001). Subgroup analysis showed that factors including area, histology, and source of the control group were significantly related to improved OS and PFS in patients with eEOC. Sensitivity analysis showed that the combined results were stable and reliable, and no significant publication bias was observed. CONCLUSIONS: Patients with eEOC can benefit from lymphadenectomy, with improved survival outcomes (OS and PFS) and a lower recurrence rate.

Meta-analysis of the efficacy of laparoscopic uterosacral ligament suspension in patients with pelvic organ prolapse.

OBJECTIVE: This study aimed to evaluate the efficacy of laparoscopic uterosacral ligament suspension (LUSLS) for pelvic organ prolapse (POP) using a meta-analysis method. METHODS: All articles about LUSLS published in English from Jan. 2010 to Jan. 2020 were retrieved using a computer from search engines, including PubMed, EMbase, Cochrane Library, CNKI, Wanfang, VIP, and Chinese Medical Journals. Meta-analysis was performed by two evaluators using RevMan 5.3 software according to the inclusion criteria. RESULTS: A total of five studies were finally included, with 361 LUSLS cases and 361 control cases. LUSLS group showed a shorter operation duration (SMD-1.96; 95% CI = -3.90- -0.03; P = 0.05), more POP-quantification system (Q) (I) (SMD1.64; 95% CI = 1.05-2.56; P = 0.03), than the control group, with significant differences. There was no difference in the complication incidence, hospital stay, POP-Q>=II between the 2 groups (P > 0.05). CONCLUSION: LUSLS was a safe and effective treatment for POP. Patients had higher postoperative satisfaction, shorter operation duration and satisfactory outcome. More high-quality randomized controlled trials are required in the future to make the results of the meta-analysis more accurate.

MoS2/Au Heterojunction Catalyst for SERS Monitoring of a Fenton-like Reaction.

Fenton technology is one of advanced oxidation process (AOP) methods to treat wastewater through chemical oxidation. Due to the limitations of classical iron-based catalysts, it is still challenging to find suitable catalysts for Fenton-like reactions. Here, MoS2/Au heterojunctions were successfully synthesized by reduction of chloroauric acid in the solution of layered MoS2 prepared by hydrothermal method. As a model molecule, methylene blue (MB) was used as the species to be degraded to evaluate the performance of the catalyst. It was determined by UV-visible spectra that the optimal catalyst can be obtained when MoS2 (mg): HAuCl4 (wt. % mL) is 2:2. The Fenton-like reaction process was monitored by introducing highly sensitive surface enhanced Raman spectroscopy (SERS). The results show that MB can be degraded by 83% in the first 10 min of the reaction, indicating that MoS2/Au has good catalytic performance. In addition, as a fingerprint spectrum, SERS was used to preliminarily analyze the molecular structure changes during the degradation process. The result showed that C-N-C bond was easier to break than the C-S-C bond. NH2 group and the fused ring were destroyed at the comparable speed at the first 30 min. In terms of application applicability, it was showed that MB degradation had exceeded 95% at all the three pH values of 1.4, 5.0, and 11.1 after the reaction was carried out for 20 min. The test and analysis of the light environment showed that the catalytic efficiency was significantly improved in the natural light of the laboratory compared to dark conditions. The possible mechanism based on ·OH and ·O2- from ESR data was proposed. In addition, it was demonstrated to be a first-order reaction from the perspective of kinetics. This study made a positive contribution to broaden of the applicable conditions and scope of Fenton-like reaction catalysts. It is expected to be used as a non-iron catalyst in practical industrial applications. From the perspective of detection method, we expect to develop SERS as a powerful tool for the in situ monitoring of Fenton-like reactions, and to further deepen our understanding of the mechanism.

Endometriosis decreases female sexual function and increases pain severity: a meta-analysis.

PURPOSE: This study aimed to explore the effects of endometriosis on female sexual function. METHODS: PubMed, Embase, and Web of Science databases were searched to analyze the Female Sexual Function Index (FSFI) or visual analog scale (VAS) scores between women with and without endometriosis. Data from publications were generated, and the sexual function of women with and without endometriosis was systematically evaluated. RESULTS: A total of six publications were included in the study. The FSFI total score and its six domains were significantly lower in women with endometriosis: FSFI total score (P < 0.001), desire (P = 0.045), arousal (P = 0.039), pain domains (P < 0.001), lubrication (P < 0.001), orgasm (P = 0.001), and satisfaction (P < 0.001). Women with endometriosis exhibited more severity in terms of VAS scores for dyspareunia (P = 0.008) and chronic pelvic pain (P < 0.001); however, no significant severity for dysmenorrhea was observed (P = 0.118). Subgroup analysis showed that the region was not a source of heterogeneity. Publication bias was not noted in all included studies, and most results of the sensitivity analysis for the included indexes were stable, which implied that our results were relatively reliable. CONCLUSION: The present meta-analysis provided evidence that endometriosis decreased female sexual function and increased the pain severity of dyspareunia and chronic pelvic pain.

New insight into enhanced transport of multi-component porous covalent-organic polymers with alkyl chains as injection agents for levofloxacin removal in saturated sand columns.

Levofloxacin (LEV) is prone to be retained in aquifers due to its strong adsorption affinity onto sand, thus posing a threat to groundwater quality. In-situ injection technology for remediating LEV-contaminated soil and groundwater is still challenging owing to the lack of appropriate remedial agents. Herein, two novel multi-component porous covalent-organic polymers (namely, SLEL-1 and SLEL-2) with alkyl chains were constructed through Schiff-base reactions to adsorb LEV from an aqueous solution, in which the kinetics, isotherms, influenced factors were investigated. Plausible adsorption mechanisms were proposed through characterization and experimental analysis, including pore filling effect, π-π electron-donor-acceptor (EDA) interaction, hydrogen bonding force, hydrophobic-hydrophobic interaction as well as electrostatic force. In addition, response surface methodology (RSM) revealed the treatment optimization and reciprocal relationship within multi-variables. Furthermore, taking advantage of favorable dispersion and outstanding competitive behavior, SLEL-1 was established as an in-situ adsorptive agent in dynamic saturated columns on a laboratory scale to investigate the removal of LEV from water-bearing stratum. Overall, the findings of this work provided an insight into the fabrication of SLELs as long-term mobile and reusable adsorptive agents for practical in-situ applications in the future.

Three porous shapeable three-component hydrogen-bonded covalent-organic aerogels as backfill materials in a simulated permeable reactive barrier (PRB) for trapping levofloxacin.

Levofloxacin (LEV) infiltrated in groundwater has threatened the safety of drinking water. For in-situ remediation of LEV-contaminated groundwater, there exists a main challenge of exploiting proper high efficient backfill medium in utilizing charming permeable reactive barriers (PRBs). Herein, three porous shapeable three-component hydrogen-bonded covalent organic aerogels (HCOA-1, HCOA-2 and HCOA-3) were fabricated based on a multiple-linking-site strategy to evaluate for adsorptive removal of LEV. The three HCOAs exhibited satisfactory performance in LEV adsorption that could integrate high adsorption capacity, good antiion interference, excellent recyclability and wide pH tolerance. The different regularity of kinetics and isotherms of three HCOAs signified that electrostatic effect, pore preservation, hydrogen bonding probably govern the adsorption process in combination, coupling with π-π electron-donor-acceptor (EDA), dipole-dipole and hydrophobic-hydrophobic interaction besides. In addition, the response surface methodology (RSM) was employed for studying the single and synergetic effects of selected variables and optimizing operation conditions. Furthermore, a laboratory PRB column packed with processable HCOA-2 was set up to investigate the LEV removal, and the breakthrough data was explained by Adams-Bohart, Thomas, BDST and Yoon-Nelson models. We believe could hopefully bring HCOAs into the real in-situ remediation of such challenging and persistent LEV-polluted groundwater with further massive-scale efficiently.

Bibliometric analysis of randomized controlled trials of colorectal cancer over the last decade.

BACKGROUND: Colorectal cancer is one of the most common cancers globally. In China, its prevalence ranks fourth and fifth among females and males, respectively. Presently, treatment of rectal cancer follows a multidisciplinary comprehensive treatment approach involving surgery, radiotherapy, chemotherapy, and targeted therapy. With deepening theoretical and molecular research on colorectal cancer, randomized controlled trials (RCTs) on colorectal cancer have made significant progress. However, many RCTs have shortfalls. AIM: To investigate the RCTs of global colorectal cancer spanning from 2008 to 2018. To provide suggestions for conducting Chinese RCTs of colorectal cancer. METHODS: PubMed and Web of Science databases were searched to obtain RCTs of colorectal cancer carried out between January 1, 2008, and January 1, 2018. The bibliometric method was used for statistical analysis of the publication years, countries/regions, authors, institutions, source journals, quoted times, key words, and authors. RESULTS: Colorectal cancer RCTs showed an upward trend between 2008 to 2018; the top 10 research institutions in the included literature were from the United States, the United Kingdom, and other countries with a high incidence of colorectal cancer. Most of the related research journals are sponsored by European and American countries. The 15 most cited studies involved international multicenter clinical research, having few participants from Chinese research institutions. Network visualization using key words showed that RCTs on colorectal cancer focus on screening, disease-free survival, drug treatment, surgical methods, clinical trials, quality of life, and prognosis. The result of the coauthorship network analysis showed that Chinese researchers are less involved in international exchanges compared to those from leading publication countries. CONCLUSION: High-quality RCTs are increasingly favored by leading international journals. However, there is still a large gap in clinical research between China and leading countries. Researchers should implement standardized and accurate clinical trials, strengthen international multicenter cooperation, and emphasize quality control.

Identification of metastasis and prognosis-associated genes for serous ovarian cancer.

Serous ovarian cancer is one of the most fatal gynecological tumors with an extremely low 5-year survival rate. Most patients are diagnosed at an advanced stage with wide metastasis. The dysregulation of genes serves an important role in the metastasis progression of ovarian cancer. Differentially expressed genes (DEGs) between primary tumors and metastases of serous ovarian cancer were screened out in the gene expression profile of GSE73168 from Gene Expression Omnibus (GEO). Cytoscape plugin cytoHubba and weighted gene co-expression network analysis (WGCNA) were utilized to select hub genes. Univariate and multivariate Cox regression analyses were used to screen out prognosis-associated genes. Furthermore, the Oncomine validation, prognostic analysis, methylation mechanism, gene set enrichment analysis (GSEA), TIMER database analysis and administration of candidate molecular drugs were conducted for hub genes. Nine hundred and fifty-seven DEGs were identified in the gene expression profile of GSE73168. After using Cytoscape plugin cytoHubba, 83 genes were verified. In co-expression network, the blue module was most closely related to tumor metastasis. Furthermore, the genes in Cytoscape were analyzed, showing that the blue module and screened 17 genes were closely associated with tumor metastasis. Univariate and multivariate Cox regression revealed that the age, stage and STMN2 were independent prognostic factors. The Cancer Genome Atlas (TCGA) suggested that the up-regulated expression of STMN2 was related to poor prognosis of ovarian cancer. Thus, STMN2 was considered as a new key gene after expression validation, survival analysis and TIMER database validation. GSEA confirmed that STMN2 was probably involved in ECM receptor interaction, focal adhesion, TGF beta signaling pathway and MAPK signaling pathway. Furthermore, three candidate small molecule drugs for tumor metastasis (diprophylline, valinomycin and anisomycin) were screened out. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot showed that STMN2 was highly expressed in ovarian cancer tissue and ovarian cancer cell lines. Further studies are needed to investigate these prognosis-associated genes for new therapy target.

Therapeutic Strategies Targeting Cancer Stem Cells and Their Microenvironment.

Cancer stem cells (CSCs) have been demonstrated in a variety of tumors and are thought to act as a clonogenic core for the genesis of new tumor growth. This small subpopulation of cancer cells has been proposed to help drive tumorigenesis, metastasis, recurrence and conventional therapy resistance. CSCs show self-renewal and flexible clonogenic properties and help define specific tumor microenvironments (TME). The interaction between CSCs and TME is thought to function as a dynamic support system that fosters the generation and maintenance of CSCs. Investigation of the interaction between CSCs and the TME is shedding light on the biologic mechanisms underlying the process of tumor malignancy, metastasis, and therapy resistance. We summarize recent advances in CSC biology and their environment, and discuss the challenges and future strategies for targeting this biology as a new therapeutic approach.

Does Circular RNA Exert Significant Effects in Ovarian Cancer?

Circular RNA, also called circRNA, is a type of widespread RNA that is mainly derived from the spliceosome, from which DNA is transcribed into messenger RNA (mRNA). CircRNAs are characterized by the formation of a covalently closed continuous loop, and they play a variety of gene regulatory roles. CircRNAs were initially thought to represent splicing errors, but an increasing amount of evidence indicates that they may play significant roles in a variety of human diseases, including cancers, cardiovascular disease, neurological disorders, and pre-eclampsia. Studies have suggested that circRNAs regulate miRNA activity that arises from miRNA-mediated sponge effects. It has been shown that CDR1as acts as a sponge for miR-7 and that a testis-specific circRNA within the sex-determining region of Y (SRY) acts as a sponge for miR-138. Because miR-7 and miR-138 modulate several oncogenes and tumor suppressor genes, the interactions between ciRS-7 and miR-7 and between SRY and miR-138 may play important roles in cancer-related pathways. Hence, currently available data suggest that circRNAs may exert significant effects on diagnoses, prognoses, and therapies in ovarian cancer.

MiR-200a-3p promoted the malignant behaviors of ovarian cancer cells through regulating PCDH9.

BACKGROUND: Increasing evidence has revealed that the aberrant expression of microRNAs (miRNAs) plays vital roles in the development and progression of ovarian cancer. MiR-200a-3p was found to act as an oncogene in a variety of cancers, however, the expression and function of miR-200a-3p in ovarian cancer has not been characterized. MATERIALS AND METHODS: The expression of miR-200a-3p in ovarian cancer tissues and cell lines was detected by the RT-qPCR. The influence of miR-200a-3p on the growth of ovarian cancer cells was determined with the Cell Counting Kit-8 assay, colony formation and cell invasion assay. The binding of miR-200a-3p with the 3'-untranslated region (UTR) of PDCH9 was detected by luciferase reporter assay. The expression of PCDH9 was investigated by RT-qPCR and Western blot analysis. RESULTS: miR-200a-3p was up-regulated in ovarian cancer tissues and cell lines. Highly expressed miR-200a-3p was significantly associated with the tumor size, tumor metastasis and TNM stage. Overexpression of miR-200a-3p markedly promoted the proliferation, colony formation and invasion of ovarian cancer cells. Functional study uncovered that miR-200a-3p bound the 3'-untranslated region (UTR) of PCDH9 and decreased the expression of PCDH9 in ovarian cancer cells. The expression of miR-200a-3p in ovarian cancer tissues was significantly negatively correlated with that of PCDH9. Restored PCDH9 inhibited the promoting effect of miR-200a-3p on the proliferation of ovarian cancer cells. CONCLUSION: Our results suggested the potential oncogenic function of miR-200a-3p via modulating PCDH9 in ovarian cancer.

Comparison of efficacy of robotic surgery, laparoscopy, and laparotomy in the treatment of ovarian cancer: a meta-analysis.

BACKGROUND: We intended to compare the clinical effect of robotic surgery with laparoscopy and laparotomy in ovarian cancer treatment. METHODS: The included studies were retrieved from PubMed, Embase, and the Cochrane Library databases. The Methodological Index for Nonrandomized Studies (MINORS) was used to evaluate the study quality. Effect measures were presented with weighted mean difference (WMD)/odds ratio (OR) and 95% confidence interval (CI), and heterogeneity test was assessed using Q test and I2 statistics to determine the use of the random effects model or fixed effects model. Egger's test was used to assess the publication bias. RESULTS: A total of eight studies was included in this meta-analysis with a MINORS score of 16-18. In the random effects model, estimated blood loss (EBL) of robotic surgery was significantly less compared with laparotomy (WMD = - 521.7027, 95% CI - 809.7816; - 233.6238). In the fixed effects model, length of hospital stay (LHS) (WMD = - 5.2225, 95% CI - 6.1485; - 4.2965) and postoperative complication (PC) (OR = 0.4710, 95% CI 0.2537; 0.8747) of robotic surgery were significantly less, and overall survival (OS) rate (OR = 6.4355, 95% CI 1.6722; 24.7678, P = 0.0070) of robotic surgery was significantly higher compared with laparotomy. There was no difference in the effect size of all variables between robotic surgery and laparoscopy. Meanwhile, a publication bias (t = 6.8290, P = 0.002405) was only identified for PC in robotic surgery and laparotomy groups; no publication bias was identified for the other variables. CONCLUSIONS: Despite the above results, it failed to show oncological safety and recurrence by pathological stages or histologic types in this meta-analysis, and those confounding factors might affect the clinical outcome. Future meta-analyses with a larger number of eligible randomized controlled trial studies were needed to determine the most suitable treatment method for patients with different stages and types of ovarian cancer.

Optimal subset of signature miRNAs consisting of 7 miRNAs that can serve as a novel diagnostic and prognostic predictor for the progression of cervical cancer.

Cervical cancer is the second most commonly diagnosed cancer in women. Novel prognostic biomarkers are required to predict the progression of cervical cancer. Cervical cancer expression data were obtained from The Cancer Genome Atlas (TCGA) database. MicroRNAs (miRNAs) significantly differentially expressed between early­ and advanced­stage samples were identified by expression analysis. An optimal subset of signature miRNAs for pathologic stage prediction was delineated using the random forest algorithm and was used for the construction of a cervical cancer­specific support vector machine (SVM) classifier. The roles of signature miRNAs in cervical cancer were analyzed by functional annotation. In total, 44 significantly differentially expressed miRNAs were identified. An optimal subset of 7 signature miRNAs was identified, including hsa­miR­144, hsa­miR­147b, hsa­miR­218­2, hsa­miR­425, hsa­miR­451, hsa­miR­483 and hsa­miR­486. The signature miRNAs were used to construct an SVM classifier and exhibited a good performance in predicting pathologic stages of samples. SVM classification was found to be an independent prognostic factor. Functional enrichment analysis indicated that these signature miRNAs are involved in tumorigenesis. In conclusion, the subset of signature miRNAs could potentially serve as a novel diagnostic and prognostic predictor for cervical cancer.

Leukocyte integrin signaling regulates FOXP1 gene expression via FOXP1-IT1 long non-coding RNA-mediated IRAK1 pathway.

Leukocyte integrin-dependent downregulation of the transcription factor FOXP1 is required for monocyte differentiation and macrophage functions, but the precise gene regulatory mechanism is unknown. Here, we identify multi-promoter structure (P1, P2, and P3) of the human FOXP1 gene. Clustering of the ß2-leukocyte integrin Mac-1 downregulated transcription from these promoters. We extend our prior observation that IL-1 receptor-associated kinase 1 (IRAK1) is physically associated with Mac-1 and provide evidence that IRAK1 is a potent suppressor of human FOXP1 promoter. IRAK1 reduced phosphorylation of histone deacetylase 4 (HDAC4) via inhibiting phosphorylation of calcium/calmodulin dependent protein kinase II delta (CaMKIIδ), thereby promoting recruitment of HDAC4 to P1 chromatin. A novel human FOXP1 intronic transcript 1 (FOXP1-IT1) long non-coding RNA (lncRNA), whose gene is embedded within that of FOXP1, has been cloned and found to bind directly to HDAC4 and regulate FOXP1 in cis manner. Overexpression of FOXP1-IT1 counteracted Mac-1 clustering-dependent downregulation of FOXP1, reduced IRAK1 downregulation of HDAC4 phosphorylation, and attenuated differentiation of THP-1 monocytic cells. In contrast, Mac-1 clustering inhibited FOXP1-IT1 expression with reduced binding to HDAC4 as well as phosphorylation of CaMKIIδ to activate the IRAK1 signaling pathway. Importantly, both IRAK1 and HDAC4 inhibitors significantly reduced integrin clustering-triggered downregulation of FOXP1 expression in purified human blood monocytes. Identification of this Mac-1/IRAK-1/FOXP1-IT1/HDAC4 signaling network featuring crosstalk between lncRNA and epigenetic factor for the regulation of FOXP1 expression provides new targets for anti-inflammatory therapeutics.

Identifying Molecular Markers of Cervical Cancer Based on Competing Endogenous RNA Network Analysis.

AIM: Recurrence being a major challenge for the treatment of cervical cancer, we aimed at identifying novel molecular markers of cervical cancer to improve recurrence prediction. METHODS: Cervical cancer samples were obtained from the Cancer Genome Atlas. Prognosis-associated long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs between recurrent and nonrecurrent samples were acquired using expression analysis. Regulatory relationships among these prognosis-associated RNAs were predicted and used to construct a competing endogenous RNA (ceRNA) network. Key prognostic lncRNAs, miRNAs, and mRNAs were identified using the ceRNA network, followed by the Kaplan-Meier survival analysis to reveal the influence of these key prognostic RNAs on prognosis. RESULTS: In total, 15 lncRNAs, 10 miRNAs, and 348 mRNAs were identified as significant prognosis-associated molecules. The cervical cancer-related ceRNA network contained 13 prognosis-associated lncRNAs, 5 prognosis-associated miRNAs, and 120 prognosis-associated mRNAs. Key prognostic lncRNAs, miRNAs, and mRNAs were further identified using the ceRNA network. The key prognostic lncRNAs included H19 and HOTAIR, those for miRNAs included hsa-miR-133b, hsa-miR-138, and hsa-miR-301b, and those for mRNAs included Wnt family member 2, fibroblast growth factor 7, fibronectin 1, synaptic vesicle glycoprotein 2A, and bone morphogenetic protein 7. CONCLUSION: The key prognostic lncRNAs, miRNAs, and mRNAs may serve as potential molecular markers for recurrence prediction and may contribute to the treatment of cervical cancer.