Circular RNAs (circRNAs) are covalently closed RNA circles without a 5 0 cap or 3 0 tail. Since the landmark discovery of ciRS-7/CDR1as functioning as a miR-7 sponge in 2013, circRNAs have become a hot topic in RNA research. CircRNAs have been found to play active roles in cancer, cardiovascular diseases, neurological disorders, and many other diseases. They can function as microRNA (miRNA) sponges, protein scaffolds, and even translation templates. However, as circRNA research expands, many divergent views have emerged. For example, are most circRNAs competent in serving as miRNA sponges? What kinds of circRNAs are most likely to sponge miRNAs? Apart from sponging miRNAs, what could the functions of most circRNAs be? What are the features of circRNAs that are translatable? Many researchers have claimed that circRNAs are abundant, stable, conserved, and specific molecules, which hold great potential in serving as biomarkers. However, circRNA abundance is variable and some circRNAs are abundant while others are not. In addition, their stability and conservation may vary under different circumstances. Furthermore, it is unclear whether circRNA biogenesis is more likely to be regulated by RNA binding proteins or transcription factors. All of these are open questions that remain to be answered by researchers in this field. Discussing and investigating these questions will advance the understanding of this class of novel molecules and may propel inspiring new ideas for future studies.

We performed this meta-analysis of epidemiologic studies to investigate the associations between circulating adiponectin, leptin and adiponectin-leptin (A/L) ratio and endometrial cancer risk. Relevant manuscripts were identified by searching PubMed and ISI Web of Science databases as well as by manual searching the references cited in retrieved manuscripts. Random-effects models were used to estimate summary odds ratio (SOR) and 95% confidence intervals (CIs) for aforementioned associations. Fourteen manuscripts with 13 studies (five nested case-control and eight case-control studies) cumulatively involving a total of 1,963 endometrial cancer cases and 3,503 noncases were included in the analyses. Overall, comparing persons with circulating concentrations of adiponectin, leptin and A/L ratio in the top tertile with persons with concentrations of these biomarkers in the bottom tertile yielded SORs of 0.47 (95% CI: 0.34-0.65; I 2 5 63.7%; n 5 13), 2.19 (95% CI: 1.44-3.31; I 2 5 64.2%; n 5 7),and 0.45 (95% CI: 0.24-0.86; I 2 5 90.1%; n 5 5), respectively. Notably, there was an 18% reduction in risk for per each 5 lg/mL increment in circulating adiponectin concentrations (SOR 5 0.82; 95% CI: 0.74-0.90; I 2 5 49%; n 5 8). Stratifying by study characteristics and whether these studies considered or adjusted for potential confounders, the findings were robust in the analyses of circulating adiponectin and leptin. No evidence of publication bias was detected. In conclusion, the findings from this metaanalysis suggest that increased circulating adiponectin and A/L ratio or decreased leptin concentrations were associated with reduced risk of endometrial cancer. Further prospective designed studies are warranted to confirm our findings.Endometrial cancer is the second most common gynecologic malignancy worldwide, with approximately 0.3 million new cases in 2012. 1 There is no doubt that obesity is a wellrecognized risk factor for this disease. Recently, the biological mechanisms linking obesity and endometrial cancer have largely centered on the aromatization of androgens in adipose tissue, leading to increased circulating estradiol levels 2 which have been the primary stimulants of endometrial proliferation. 3 However, this mechanism cannot fully explain the incidence of endometrial cancer in obese women. Experimental studies have provided evidence that adipokines, which are associated with hyperinsulinemia and degree of insulin resistance independent of adiposity, are also involved in the development of endometrial cancer.Adipose tissue was previously considered to be an energystorage site. During recent decades, this tissue has been found to be an endocrine organ producing and secreting several bioactive peptides, including adipokines such as adiponectin and leptin. 4 Biological studies have shown that adiponectin, the most abundant adipokine, is not only inversely associated with obesity as well as hyperinsulinemia 5,6 but appears to have anti-inflammatory, antiangiogenic and antidiabetic properties 7,8 ; In contrast,...

Evidence between age at menarche and endometrial cancer risk have been controversial. Therefore, we conducted a meta-analysis of prospective studies to analyze the aforementioned association. Relevant studies were identified by searching PubMed and EMBASE databases until the end of June 2015. A random-effects model was used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs) for associations between menarcheal age and endometrial cancer risk. Our meta-analysis included eight prospective studies involving 4553 subjects with endometrial cancer. The summarized RRs of endometrial cancer for menarcheal age were 0.68 (95%CI = 0.58–0.81, I2 = 41.9%, P = 0.099, n = 8) when comparing women with oldest category of menarcheal age with women with youngest category of menarcheal age. Notably, there was an 4% reduction in risk for per 2 years delay in menarcheal age (summarized RR = 0.96; 95%CI = 0.94–0.98, I2 = 45.7%, P = 0.101, n = 6). Additionally, significant inverse associations were consistent within all stratified analyses. There was no evidence of publication bias or significant heterogeneity between subgroups detected by meta-regression analyses. Our findings support the hypothesis that late menarcheal age is inversely associated with endometrial cancer risk. Further larger prospective or pooled studies are warranted to fully adjust for potential confounders and distinguish whether the associations differ by histological subtypes of endometrial cancer.

BackgroundEndometrial cancer (EC) is one of the three major gynecological malignancies. Numerous biomarkers that may be associated with survival and prognosis have been identified through database mining in previous studies. However, the predictive ability of single-gene biomarkers is not sufficiently specific. Genetic signatures may be an improved option for prediction. This study aimed to explore data from The Cancer Genome Atlas (TCGA) to identify a new genetic signature for predicting the prognosis of EC.MethodsmRNA expression profiling was performed in a group of patients with EC (n = 548) from TCGA. Gene set enrichment analysis was performed to identify gene sets that were significantly different between EC tissues and normal tissues. Cox proportional hazards regression models were used to identify genes significantly associated with overall survival. Quantitative real-time-PCR was used to verify the reliability of the expression of selected mRNAs. Subsequent multivariate Cox regression analysis was used to establish a prognostic risk parameter formula. Kaplan–Meier survival estimates and the log‐rank test were used to validate the significance of risk parameters for prognosis prediction.ResultNine genes associated with glycolysis (CLDN9, B4GALT1, GMPPB, B4GALT4, AK4, CHST6, PC, GPC1, and SRD5A3) were found to be significantly related to overall survival. The results of mRNA expression analysis by PCR were consistent with those of bioinformatics analysis. Based on the nine-gene signature, the 548 patients with EC were divided into high/low-risk subgroups. The prognostic ability of the nine-gene signature was not affected by other factors.ConclusionA nine-gene signature associated with cellular glycolysis for predicting the survival of patients with EC was developed. The findings provide insight into the mechanisms of cellular glycolysis and identification of patients with poor prognosis in EC.

The association between parity and endometrial cancer risk is inconsistent from observational studies. We aimed to quantitatively assess the relationship by summarizing all relevant epidemiological studies. PubMed (MEDLINE), Embase and Scopus were searched up to February 2015 for eligible case–control studies and prospective studies. Random-effects model was used to pool risk estimations. Ten prospective studies, 35 case-control studies and 1 pooled analysis of 10 cohort and 14 case-control studies including 69681 patients were identified. Pooled analysis revealed that there was a significant inverse association between parity and risk of endometrial cancer (relative risk (RR) for parous versus nulliparous: 0.69, 95% confidence interval (CI) 0.65–0.74; I2 = 76.9%). By evaluating the number of parity, we identified that parity number of 1, 2 or 3 versus nulliparous demonstrated significant negative association (RR = 0.73, 95% CI 0.64–0.84, I2 = 88.3%; RR = 0.62, 95% CI 0.53–0.74, I2 = 92.1%; and RR = 0.68, 95% CI 0.65–0.70, I2 = 20.0% respectively). The dose-response analysis suggested a nonlinear relationship between the number of parity and endometrial cancer risk. The RR decreased when the number of parity increased. This meta-analysis suggests that parity may be associated with a decreased risk of endometrial cancer. Further studies are warranted to replicate our findings.

Background/Aims: Elucidation of the molecular mechanisms underlying ovarian cancer (OC) cell invasion and migration may provide important evidence for developing efficient therapy. Recently, Matrix metalloproteinase (MMP) has been shown to be regulated by vascular endothelial growth factor family members, especially placental growth factor (PLGF), as a potential mechanism underlying cancer invasion. Here, we studied the molecular relationship between PLGF and MMP7 in the OC. Methods: We examined the levels of PLGF and MMP7 in the resected OC specimens and compared to paired adjacent non-tumor ovarian tissue. We also examined the correlation between PLGF and MMP7. We modified PLGF levels in a human OC cell line, OVCAR3, and analyzed the effects on MMP7. Prediction of microRNA (miRNA) binding to 3'-UTR of MMP7 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay using miR-543-modifed OC cells. The levels of miR-543 were examined in the OC specimens, and the correlation between miR-543 and PLGF or MMP7 was performed. Results: PLGF and MMP7 both significantly increased in the OC specimens, compared to paired adjacent non-tumor ovarian tissue. PLGF significantly increased MMP7 in the OC cells at protein level, but not at mRNA level. In OC cells, PLGF significantly decreased the levels of miR-543, which suppressed the translation of MMP7 mRNA via 3'-UTR binding. In OC specimen, miR-543 significantly decreased, compared to paired adjacent non-tumor ovarian tissue. An inverse correlation was detected between the levels of miR-543 and PLGF or MMP7 in the OC specimens. Conclusion: MiR-543 inhibits translation of MMP7 through binding to the 3'-UTR of MMP7 mRNA in OC. PLGF suppresses miR-543, which activates MMP7-mediated cancer invasion.

Mass screening with a reverse passive hemagglutination fecal occult blood test along with an individual attributive degree value score was effective in reducing mortality from rectal cancer but not in reducing mortality from colon cancer or the incidence of colorectal cancer.

No abstract