Downregulating lncRNA NEAT1 induces proliferation and represses apoptosis of ovarian granulosa cells in polycystic ovary syndrome via microRNA-381/IGF1 axis.

OBJECTIVE: Researchers have revealed the combined functions of long noncoding RNAs (lncRNAs) and microRNA (miRNAs) in polycystic ovary syndrome (PCOS). This study aimed to understand the role of nuclear-enriched abundant transcript 1 (NEAT1) and miR-381 involving insulin-like growth factor 1 (IGF1) in PCOS. METHODS: PCOS rat model was established by dehydroepiandrosterone induction. NEAT1, miR-381 and IGF1 expression in ovarian granulosa cells of PCOS patients and ovarian tissues of PCOS rats were tested. Bioinformatics website and dual luciferase reporter gene assay were utilized to verify the relationship between NEAT1 and miR-381 and that between miR-381 and IGF1. Levels of sex hormone, pathological changes and ovarian granulosa cell apoptosis in ovarian tissues of PCOS rats were detected. Ovarian granulosa cell proliferation and apoptosis were analyzed in vitro. RESULTS: NEAT1 and IGF1 expression increased while miR-381 expression decreased in the ovarian granulosa cells of patients with PCOS and the ovarian tissues of PCOS rats. In in vivo experiments, interference with NEAT1 improved the levels of sex hormones, alleviated pathological changes and suppressed ovarian granulosa cell apoptosis in the ovarian tissues of PCOS rats. In in vitro cell experiments, interference with NEAT1 suppressed apoptosis and enhanced cell proliferation of ovarian granulosa cells. NEAT1 interference-mediated effect would be reversed by up-regulating miR-381. NEAT1 acted as a ceRNA to adsorb miR-381 to target IGF1. Overexpression of IGF1 reversed the inhibitory effect of miR-381 on ovarian granulosa cell apoptosis. CONCLUSION: Interference with NEAT1 increases miR-381 and reduces IGF1 levels, effectively improving the levels of sex hormones and reducing the pathological damage of ovarian tissue in rats with PCOS.

Association Between Arg72Pro Polymorphism in TP53 and Malignant Abdominal Solid Tumor Risk in Hunan Children.

Pediatric solid tumors are heterogeneous and comprise various histological subtypes. TP53, a tumor suppressor, orchestrates the transcriptional activation of anti-cancer genes. The gene coding for this protein is highly polymorphic, and its mutations are associated with cancer development. The Arg72Pro polymorphism in TP53 has been associated with susceptibility to various types of cancer. Here, in this hospital-based study, we evaluated the association of this polymorphism with susceptibility toward malignant abdominal solid tumors in children in the Hunan province of China. We enrolled 162 patients with neuroblastoma, 60 patients with Wilms' tumor, and 28 patients with hepatoblastoma as well as 270 controls. Genotypes were determined using a TaqMan assay, and the strength of the association was assessed using an odds ratio, within a 95% confidence interval identified using logistic regression models. Our results showed that the Arg72Pro polymorphism did not exhibit significant association with susceptibility toward pediatric malignant abdominal solid tumors. Stratification analysis revealed that this polymorphism exerts weak sex- and age-specific effects on Wilms' tumor and hepatoblastoma susceptibility, respectively. Overall, our results indicate that the Arg72Pro polymorphism may have a marginal effect on susceptibility toward pediatric malignant abdominal solid tumors in Hunan, and this finding warrants further confirmation.

The role of long noncoding RNAs in regulating invasion and metastasis of malignant tumors.

Long noncoding RNAs (lncRNAs) are a group of non-protein-coding transcripts exceeding 200 nucleotides in length, which are emerging as key players in various fundamental biological processes. Furthermore, it is increasingly recognized that mutation and dysregulation of lncRNAs contribute importantly to a variety of human diseases, particularly human cancers. Previous studies have revealed that altered lncRNAs have a close association with tumorigenesis, metastasis, prognosis and diagnosis of cancers. The present review aims to exhibit a brief overview of the associated reports of lncRNAs in cancers, including colorectal cancer, gastric cancer, lung adenocarcinoma, nasopharyngeal carcinoma, cervical cancer and esophageal cancer. Altogether, we argue that lncRNAs have potential as new biomarkers in cancer prognosis and diagnosis, and as promising therapeutic targets for the prevention and treatment of human cancers.

Melanotic neuroectodermal tumor of infancy in ovary: A rare case report.

RATIONALE: Melanotic neuroectodermal tumor of infancy (MNTI) is an extremely rare benign pigmented neoplasm of neural crest origin with rapid expansile growth and a high recurrence rate. It is predominantly found in infants of <1 year of age, involvement of the head-and-neck region is the most common presentation though it is reported at other sites including mediastinum, shoulder, thigh, foot, epididymis, uterus and ovary. The patient reported here is the third case of MNTI presenting in an ovary, and the first reported in the infant ovary. PATIENT CONCERNS: A 33-month-old girl was presented to our unit for a huge abdominal mass. DIAGNOSIS: MNTI was eventually diagnosed by histological manifestations supplemented with immunohistochemical findings. INTERVENTIONS: Exploratory laparotomy and complete resection were conducted successfully. OUTCOMES: Postoperative course was uneventful and no recurrence was displayed in the 6-month follow-up. LESSONS: This case emphasizes that pediatric surgeons and pathologists must always consider the possibility of MNTI while dealing with ovarian neoplasms in infants. Although considered to be a benign tumor, proper treatment and close clinicoradiological follow-up of this tumor are of great importance.

H19 gene polymorphisms and neuroblastoma susceptibility in Chinese children: a six-center case-control study.

Neuroblastoma is the most common seen solid tumor in children less than one year old. Given that polymorphisms in the lncRNA H19 gene are observed in several types of human malignancies, there likely to be similar events that contribute to the pathogenesis of neuroblastoma. We hypothesize that single nucleotide polymorphisms (SNPs) in the H19 gene might predispose to neuroblastoma. Here, we genotyped three SNPs (rs2839698 G>A, rs3024270 C>G, rs217727 G>A) from H19 gene in a Chinese population (700 subjects with neuroblastoma and 1516 control subjects) enrolled from six hospitals and examined the effect of individual and combined SNPs on the risk of neuroblastoma. Odds ratios (ORs) and 95% confidence intervals (CIs) calculated from logistic regression were adopted to assess such association, adjusted for age and gender. Among them, 700 controls and 1514 cases were successfully genotyped. None of these three SNPs were found to be relevant to the risk of neuroblastoma, either in overall analysis or stratification analysis. Findings from this study excluded the participation of lncRNA H19 gene SNPs in the risk of neuroblastoma. More independent case-control studies are encouraged to better elucidate this relationship.

miR-34b/c rs4938723 T>C Decreases Neuroblastoma Risk: A Replication Study in the Hunan Children.

Neuroblastoma is the most common seen solid neural tumor in children less than age one. As mutation in the miR-34b/c gene is observed in several types of human malignancies, there likely to be similar events that contribute to the pathogenesis of neuroblastoma. We hypothesize that polymorphism in the miR-34b/c gene might predispose to neuroblastoma. Here, we conducted this replication study by genotyping rs4938723 T>C from miR-34b/c in Hunan children (162 subjects with neuroblastoma and 270 control subjects) and examined its effect on the risk of neuroblastoma. We determined such association using logistic regression, adjusted for age and gender. Relative to those with TT genotype, subjects with C allele had reduced neuroblastoma risk (TC vs. TT: adjusted OR = 0.46, 95%CI = 0.30-0.71; additive model: adjusted OR = 0.64, 95%CI = 0.47-0.88; TC/CC vs. TT: adjusted OR = 0.49, 95%CI = 0.33-0.73). Stratified analysis revealed that rs4938723 TC/CC carriers were less likely to develop neuroblastoma for patients in the subgroups of age ≤ 18 months, age > 18 months, females, males, tumors in retroperitoneal, tumors in other sites, and clinical stages II, III, IV, and III+IV. Our findings verified miR-34b/c rs4938723 C variant allele as a protective factor for the risk of neuroblastoma. Further investigation of how miR-34b/c rs4938723 T>C might modify neuroblastoma risk is warranted.

Status of External Quality Assessment on Tumor Markers in China.

BACKGROUND: The nationwide external quality assessment (EQA) of tumor markers in China has been launched for years. The quality of the performance of Chinese clinical laboratories on tumor markers is partly reflected through analysis of EQA results. This report presents an 8-year EQA result of the six most common tumor markers from 2006 to 2013. METHODS: Ten freeze-dried EQA samples were distributed to participants every year. Satisfactory performance was defined as scores of more than 80% of acceptable responses with the evaluation criterion of ± 25%. The robust coefficient of variability (CV) between laboratories and percentage difference against the target value of each sample were also calculated by year. RESULTS: A total number of 1154 laboratories submitted results in 2013, which was more than threefold of 2006. The proportion of laboratories with satisfactory performance showed an overall rising trend over the years and was up to 95% for the second survey in 2013. The overall decrease of robust CV was observed for all analytes including alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), total prostate specific antigen (t-PSA), cancer antigen 125 (CA 125), cancer antigen 15-3 (CA 15-3), and cancer antigen 19-9 (CA 19-9) except for CEA, which exhibited a rise followed by a flat trend. The percentage difference narrowed gradually and was less than 2% in 2013. CONCLUSIONS: The 8-year EQA results showed a significant enhancement of degree of harmonization of tumor markers in China. However, standardization among various testing systems and improvement of harmonization has yet to be achieved.

[Application of damage control surgery in serious pediatric abdominal surgery].

OBJECTIVE: Damage control surgery (DCS) deals with the complex surgical problems by stages. This study investigated the application of DCS in serious pediatric abdominal surgery. METHODS: The clinical data of 49 children with serious abdominal diseases (age: 4 months to 10 years) were retrospectively studied. Of them, 32 children underwent damage control surgery (DCS) and 17 children underwent conventional operation. The preoperative critical severity score (CSS), postoperative temperature, blood pH and prothrombin time (PT), and the treatment outcome were compared between the DCS and the conventional operation groups. RESULTS: No significant difference was found in the preoperative CSS between the two groups. There were significant differences in postoperative blood pH and PT values between the two groups (p<0.05). As for postoperative temperature, there was no statistical difference between the two groups, yet the tendency of temperature recovery in the DCS group was milder than that in the conventional operation group. Twenty-seven children (84.4%) were successfully cured in the DCS group, while 9 children (52.9%) in the conventional operation group (p<0.05). CONCLUSIONS: The curative effect of DCS surpasses the conventional operation in children with serious abdominal diseases, suggesting that DCS is of value in the management of serious pediatric abdominal diseases.