Long non-coding RNA NRSN2-AS1 promotes ovarian cancer progression through targeting PTK2/ß-catenin pathway.

As a common malignant tumor among women, ovarian cancer poses a serious threat to their health. This study demonstrates that long non-coding RNA NRSN2-AS1 is over-expressed in ovarian cancer tissues using patient sample and tissue microarrays. In addition, NRSN2-AS1 is shown to promote ovarian cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, NRSN2-AS1 stabilizes protein tyrosine kinase 2 (PTK2) to activate the ß-catenin pathway via repressing MG-53-mediated ubiquitinated degradation of PTK2, thereby facilitating ovarian cancer progression. Rescue experiments verify the function of the NRSN2-AS1/PTK2/ß-catenin axis and the effects of MG53 on this axis in ovarian cancer cells. In conclusion, this study demonstrates the key role of the NRSN2-AS1/PTK2/ß-catenin axis for the first time and explores its potential clinical applications in ovarian cancer.

The diagnostic value of the combination of hemoglobin, CA199, CA125, and HE4 in endometriosis.

BACKGROUND: We aimed to analyze the differences in the peripheral blood cells and tumor biomarkers between the patients with endometriosis and healthy people, and establish a more efficient combined diagnostic model. METHODS: We retrospectively analyzed the differences in the peripheral blood cells and tumor biomarkers between the patients with endometriosis and healthy people. Binary logistic regression analysis was used to establish a combined diagnostic model. We plotted the receiver operator characteristic (ROC) curve to analyze the diagnostic efficiency of different diagnostic indexes. RESULTS: Compared with patients in the control group, patients in the endometriosis group had significantly lower eosinophil% (p = 0.045), neutrophil (p = 0.001), lymphocyte (p < 0.001), red blood cells (RBCs) (p < 0.001), and hemoglobin (HGB) (p < 0.001), and had significantly higher monocyte% (p = 0.008), monocyte-to-lymphocyte ratio (MLR) (p = 0.001), platelet-to-lymphocyte ratio (PLR) (p < 0.001), carbohydrate antigen (CA)-199 (p < 0.001), CA125 (p < 0.001), human epididymis protein (HE)-4 (p < 0.001), and the risk of ovarian malignancy algorithm (ROMA) (p < 0.001). The combined diagnostic model of HGB, CA199, CA125, and HE4 was established by binary logistic regression analysis. The ROC curve showed that the combined diagnostic model reached a sensitivity of 85.4%, a specificity of 78.83%, and an area under the curve of 0.900, which was significantly higher than that of the individual index in endometriosis diagnosis. CONCLUSION: The combined diagnostic model of HGB, CA199, CA125, and HE4 may provide a new approach for the early non-invasive diagnosis of endometriosis.

Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses.

It is well established that embryonic chromosomal abnormalities (both in the number of chromosomes and the structure) account for 50% of early pregnancy losses. However, little is known regarding the potential differences in the incidence and distribution of chromosomal abnormalities between patients with sporadic abortion (SA) and recurrent pregnancy loss (RPL), let alone the role of submicroscopic copy-number variations (CNVs) in these cases. The aim of the present study was to systematically evaluate the role of embryonic chromosomal abnormalities and CNVs in the etiology of RPL compared with SA. Over a 3-year period, 1556 fresh products of conception (POCs) from miscarriage specimens were investigated using single nucleotide polymorphism array (SNP-array) and CNV sequencing (CNV-seq) in this study, along with further functional enrichment analysis. Chromosomal abnormalities were identified in 57.52% (895/1556) of all cases. Comparisons of the incidence and distributions of chromosomal abnormalities within the SA group and RPL group and within the different age groups were performed. Moreover, 346 CNVs in 173 cases were identified, including 272 duplications, 2 deletions and 72 duplications along with deletions. Duplications in 16q24.3 and 16p13.3 were significantly more frequent in RPL cases, and thereby considered to be associated with RPL. There were 213 genes and 131 signaling pathways identified as potential RPL candidate genes and signaling pathways, respectively, which were centered primarily on six functional categories. The results of the present study may improve our understanding of the etiologies of RPL and assist in the establishment of a population-based diagnostic panel of genetic markers for screening RPL amongst Chinese women.

Prognostic value of preoperative serum bilirubin levels in ovarian cancer.

Bilirubin is a promising prognostic factor for non-liver disease-related deaths in various cancers. We investigated the association between preoperative serum bilirubin levels and oncological outcomes in patients with ovarian cancer. We retrospectively analyzed the clinical data of 282 patients with epithelial ovarian carcinoma (EOC), and grouped them according to optimal threshold values of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBL) measured by receiver operating characteristic curve analysis. Univariate and multivariate Cox proportional hazards regression analyses were used to evaluate various parameters that might affect overall survival (OS) and progression-free survival (PFS) in patients with EOC. The optimal cutoff values for TBIL, DBIL, and IBIL levels were 9.65 µmol/L, 2.95 µmol/L, and 6.75 µmol/L, respectively. Increased TBIL, DBIL, and IBIL levels correlated with the serum carbohydrate antigen (CA)-125 levels, International Federation of Gynecology and Obstetrics stage, and pathological differentiation (all P<0.05). Univariate analysis revealed longer OS and PFS in patients with high TBIL (≥9.65 µmol/L) and IBIL (≥6.75 µmol/L) levels (P<0.05). Multivariate analysis showed that patients with high IBIL levels (≥6.75 µmol/L) had significantly longer OS and PFS than those with low IBIL levels (<6.75 µmol/L) [hazard ratio (HR) = 0.333, 95% confidence interval (CI): 0.123~0.904, P<0.05; HR = 1.814, 95% CI: 1.169~2.816, P<0.05]. Therefore, IBIL is a potential independent prognostic factor for OS and PFS in patients with EOC. The higher the IBL level, the better the prognosis of patients with EOC.

Biological Function and Mechanism of Long Noncoding RNAs Nuclear-Enriched Abundant Transcript 1 in Development of Cervical Cancer.

BACKGROUND: Accumulating documents have demonstrated that long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis. As an lncRNA, nuclear-enriched abundant transcript 1 (NEAT1) has been identified to be involved in the progression of many types of cancers. However, the biological function of NEAT1 in cervical cancer is not fully investigated. The aim of this study was to disclose the specific biological function of lncRNA NEAT1 in cervical cancer progression. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to identify the expression of lncRNA NEAT1 in the cervical cancer tissues and cell lines. All cervical cancer samples used in this study were collected from the Affiliated Suzhou Hospital of Nanjing Medical University between September 2012 and September 2017. The correlation between NEAT1 expression and the overall survival rate of cervical cancer patients was analyzed by Kaplan-Meier analysis. The effects of NEAT1 knockdown or overexpression on cell proliferation were tested by performing MTT assays and colony formation assays. Transwell assays were conducted to detect the migratory ability of cervical cancer cells, in which NEAT1 was silenced or overexpressed. Western blotting was utilized to validate whether NEAT1 promotes cervical cancer progression through activating PI3K-Akt signaling pathway. RESULTS: High expression of NEAT1 predicted poor prognosis of cervical cancer patients (χ2 = 0.735, P = 0.005). Knockdown of NEAT1 decreased the number of colonies in CaSki cell from 136.667 ± 13.503 to 71.667 ± 7.506 (t = -18.76, P = 0.003) and decreased the number of colonies in HeLa cell from 128.667 ± 13.317 to 65.667 ± 7.024 (t = -5.54, P = 0.031). However, overexpression of NEAT1 increased the number of colonies in SiHa cell from 84.667 ± 12.014 to 150.667 ± 18.037 (t = 7.27, P = 0.018). Knockdown of NEAT1 decreased the migratory number of CaSki cell from 100.333 ± 9.866 to 58.333 ± 5.859 (t = -8.08, P = 0.015) and reduced the migratory number in HeLa cell from 123.667 ± 12.097 to 67.667 ± 7.095 (t = -6.03, P = 0.026). Overexpression of NEAT1 increased the migratory number of SiHa cell from 127.333 ± 16.042 to 231.333 ± 31.786 (t = 4.92, P = 0.039). CONCLUSION: NEAT1 may exert oncogenic function in cervical cancer and serve as a novel therapeutic target for cervical cancer.