Circular PVT1 regulates cell proliferation and invasion via miR-149-5p/FOXM1 axis in ovarian cancer.

Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) is a dysregulated gene in malignancy and is associated with oncogenesis. In this study, we found PVT1 RNA was an ovarian specific expressing gene, and overexpressed in multiple cancer types, including ovarian cancer (OV). Higher expression levels of PVT1 are related to shorter survival time in OV patients, especially in patients with advanced stage and grade. Recent studies indicated circular PVT1 also had an important role in cancer progression, whose roles in OV remain unclear. Knockdown of circular PVT1 significantly suppressed OV cell proliferation, migration and invasion. Bioinformatics analysis demonstrated that circular PVT1 was involved in regulating angiogenesis, osteoblast differentiation, regulation of cell growth, type B pancreatic cell proliferation, negative regulation of apoptotic process, phospholipid homeostasis, regulation of neurogenesis, definitive hemopoiesis, cell migration, regulation of glucose metabolic process, central nervous system development and type 2 immune response. Our data showed miR-149-5p targeted FOXM1, which was regulated by circular PVT1. Forkhead Box M1 (FOXM1) expression in ovarian cancer exhibited high level when compared with normal tissues, and had relation with relatively poor survival. FOXM1 promoted cell viability and reduced FOXM1 could rescue circular influence of circular PVT1-caused carcinoma induction. In conclusion, circular PVT1 increased FOXM1 level via binding to miR-149-5p and thus affected ovarian cancer cell viability and migration.

High expression of fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is a fatal form of ovarian cancer. Previous studies indicated some potential biomarkers for clinical evaluation of HGSOC prognosis. However, there is a lack of systematic analysis of different expression genes (DEGs) to screen and detect significant biomarkers of HGSOC. METHODS: TCGA database was conducted to analyze relevant genes expression in HGSOC. Outcomes of candidate genes expression, including overall survival (OS) and progression-free survival (PFS), were calculated by Cox regression analysis for hazard rates (HR). Histopathological investigation of the identified genes was carried out in 151 Chinese HGSOC patients to validate gene expression in different stages of HGSOC. RESULTS: Of all 57,331 genes that were analyzed, FAP was identified as the only novel gene that significantly contributed to both OS and PFS of HGSOC. In addition, FAP had a consistent expression profile between carcinoma-paracarcinoma and early-advanced stages of HGSOC. Immunological tests in paraffin section also confirmed that up-regulation of FAP was present in advanced stage HGSOC patients. Prediction of FAP network association suggested that FN1 could be a potential downstream gene which further influenced HGSOC survival. CONCLUSIONS: High-level expression of FAP was associated with poor prognosis of HGSOC via FN1 pathway.

The Effect of HER2 Single Nucleotide Polymorphisms on Cervical Cancer Susceptibility and Survival in a Chinese Population.

Background: Cervical cancer (CCa) is a multifactorial gynecologic disease worldwide. Effects of HER2 polymorphisms, especially those in exonic region, have been investigated in many gynecologic diseases. In this study, we evaluated the influence of functional HER2 polymorphisms on susceptibility and survival of CCa in a Chinese population. Methods: We genotyped the HER2 exonic polymorphisms by TaqMan in both case-control study (413 CCa patients vs. 396 controls) and survival study (413 CCa patients). Logistic regression and Cox regression were adopted to evaluate the genetic association with the risk and outcomes of CCa, respectively. Results: In the case-control study, there was no significant difference between patients and controls in either HER2 rs1136201 or rs1058808. However, when combined, these two polymorphisms demonstrated a significant hazardous effect for CCa (P = 0.012). Besides, number of variants was also influential (P trend =0.002). In survival analysis, dominant model of rs1136201 and co-dominant modelof rs1058808 were significantly associated with the survival (P = 0.037 and P =0.028). The combination of rs1136201 and rs1058808 also negatively impacted CCa survival (P = 0.009). Cox regression further revealed the significance of the polymorphism combination (ß = 0.38, P = 0.025, HR= 1.47, 95%CI = 1.05-2.05). Functional assay of these polymorphisms demonstrated that rs1058808 G allele was associated with stronger expression of HER2 gene. Conclusions: Our results suggested that the combination of HER2 rs1136201and rs1058808 was significantly associated with the susceptibility of CCa. Besides, this combination of polymorphism s also substantially impacted the survival of CCa patients.

Correlations between lncRNA-SOX2OT polymorphism and susceptibility to breast cancer in a Chinese population.

AIM: We evaluated the effect of lncRNA SOX2OT expression and its SNP in tumorigenesis and development of breast cancer (BC) in a case-control study. METHODS: A total of 1106 individuals, 505 newly diagnosed BC patients and 601 age-matched controls (±2 years) were testified. Real-time PCR was adopted for testing tissues' SOX2OT expression. Genotyping of rs9839776 were conducted by using SNaPshot assays. RESULTS: SOX2OT were overexpressed in BC tissues (p < 0.001). SOX2OT SNP rs9839776 was strongly associated with the higher expression of SOX2OT and an increased risk of BC in Chinese women (odds ratio: 1.42; 95% CI: 1.06-1.90; p = 0.018). CONCLUSION: These results confirmed that BC was conspicuously associated with higher SOX2OT expression. SOX2OT SNP rs9839776 was significantly associated with the onset of BC possibly via influencing the expression of SOX2OT.