B3GNT3 acts as a carcinogenic factor in endometrial cancer via facilitating cell growth, invasion and migration through regulating RhoA/RAC1 pathway-associated markers.

BACKGROUND: Aberrant expression of beta-1,3-N-acetylglucosaminyltransferase-3 (B3GNT3) has been frequently clarified in various cancers, however, its role in endometrial cancer (EC) has not been assessed in detail. PURPOSE: This study aimed to investigate the biological role of B3GNT3 in EC and simply explored the detailed mechanism. METHODS: The EC RNA-Seq dataset from TCGA database was applied to evaluate the expression of B3GNT3 and assess its role on prognostic value. HEC-1-A and KLE cell lines of EC were used to perform loss- and gain-of-function B3GNT3 assays respectively. Quantitative real-time PCR (qRT-PCR) and western blot were used to measure the mRNA and protein levels of indicated molecules respectively. Cell counting kit-8, clone formation tests, and Transwell assay served to determine the changes of proliferative, invasive and migratory abilities of EC cells after altering the expression of B3GNT3. RESULTS: B3GNT3 was found to be highly expressed in EC tissues compared to normal tissues according to the online public databases, which confirmed by the following qRT-PCR in 3 EC cell lines. Besides, high B3GNT3 expression presented a worse overall survival in EC patients as compared with low B3GNT3 expression group. Furthermore, functional experiments in vitro indicated that B3GNT3 could facilitate the cell growth, invasion and migration. Moreover, we found that downregulation of B3GNT3 significantly reduced the expression level of GTP-RhoA and GTP-RAC1, whereas upregulation of B3GNT3 presented the opposite results. CONCLUSION: The results of current study demonstrate that B3GNT3 acts as an oncogene that promotes EC cells growth, invasion and migration possibly through regulating the RhoA/RAC1 signaling pathway-related markers, suggesting that B3GNT3 may be a candidate biomarker for EC therapeutic intervention.

Upregulation of lncRNA DARS-AS1 accelerates tumor malignancy in cervical cancer by activating cGMP-PKG pathway.

This paper investigates the function of lncRNA DARS-AS1 in cervical cancer (CC) as well as its in-depth mechanism. The differential expression of DARS-AS1 and ATP1B2 were analyzed based on The Cancer Genome Atlas and the Genotype-Tissue Expression databases, and the survival rate was measured using Kaplan-Meier survival analysis. Biological function experiments were performed to detect cell proliferation, invasion, and migration. Quantitative real-time polymerase chain reaction was carried out to detect the expression of DARS-AS1 and ATP1B2. Western blot analysis was utilized to assess the protein levels of ATP1B2 and cGMP-PKG pathway-related proteins. DARS-AS1 was expressed at high levels in CC tissues and cell lines, and high expression of DARS-AS1 indicated a lower survival rate. CCK-8 and colony formation assays revealed that the overexpression of DARS-AS1 promoted the proliferation of CC cells. Furthermore, bioinformatics analysis suggested that the cGMP-PKG pathway ranks as the first pathway enriched by the differential genes that correlated with DARS-AS1 (|r| > 0.4). ATP1B2, as a cGMP-PKG pathway-related gene, was significantly correlated with the overall survival of CC patients. We further confirmed that ATP1B2 was lowly expressed in CC and negatively correlated with the DARS-AS1 expression. Then, biological function experiments exhibited that the promotion of cell proliferation, invasion, and migration resulted due to the upregulation of DARS-AS1 could be canceled by ATP1B2 overexpression. Finally, Western blot revealed that upregulation of DARS-AS1 could activate the cGMP-PKG pathway, while overexpression of ATP1B2 reversed this activation. Our study revealed that DARS-AS1/ATP1B2 contributes to regulating the progression of CC at least partially by modulating the cGMP-PKG pathway.

First trimester serum PAPP-A is associated with placenta accreta: a retrospective study.

PURPOSE: Our objective of this study was to investigate whether first trimester serum pregnancy-associated plasma protein-A (PAPP-A) differed amongst pregnancies with placenta previa-accreta and non-adherent placenta previa and healthy pregnancies by a retrospective cohort analysis. METHODS: A total of 177 pregnant females were included in the study, as follows: 35 cases of placenta previa-accreta, 30 cases of non-adherent placenta previa, and 112 cases of BMI and age matched, healthy pregnant controls. PAPP-A multiples of the median (MoM) were acquired from laboratory data files in 1 January 2017-30 September 2019. The probable maternal serum biochemical predictor of placenta accreta was analyzed by using multiple logistic regression analysis. RESULTS: PAPP-A MoM of placenta previa-accreta group was significantly higher than those of the non-adherent placenta previa group and control group (p = 0.009 < 0.05, p < 0.001). Serum PAPP-A was found to be significantly positively associated with placenta accreta after adjusted gestational week at time of blood sampling, BMI, age, smoking, and previous cesarean section history (OR: 3.51; 95% CI: 1.77-6.94; p = 0.0003 < 0.05). In addition, smoking (OR: 9.17; 95% CI: 1.69-49.62; p = 0.010 < 0.05) and previous cesarean section history (OR: 2.75; 95% CI: 1.23-6.17; p = 0.014 < 0.05) were also significantly associated with placenta accreta. CONCLUSION: Increased first trimester serum PAPP-A was significantly positively associated with placenta accreta, suggesting that the potential role of PAPP-A in identifying pregnancies at high risk for placenta accreta. Smoking and previous cesarean section history may be the risk factors for accreta in placenta previa patients.

First trimester serum PIGF is associated with placenta accreta.

OBJECTIVES: In this retrospective study, we investigated whether first trimester serum placental growth factor (PIGF) differed amongst pregnancies with placenta previa-accreta and non-adherent placenta previa and healthy pregnancies. METHODS: In 1 January 2017-30 September 2019, a total of 177 pregnant females were included in the study, as follows: 35 cases of placenta previa-accreta, 30 cases of non-adherent placenta previa, and 112 cases of age and BMI-matched, healthy pregnant controls. PIGF multiples of the median (MoM) were acquired from laboratory data files. The predictor of placenta accreta was analyzed by using multiple logistic regression analysis. RESULTS: PIGF MoM of placenta previa-accreta group was significantly higher than those of the non-adherent placenta previa group and control group (p = 0.0098 < 0.01, p = 0.0002 < 0.01). Serum PIGF was found to be significantly positively associated with placenta accreta after adjusted gestational week at time of blood sampling, BMI, and age (OR: 4.83; 95% CI: 1.91-12.24；p = 0.0009 < 0.01). In addition, previous cesarean section history (OR: 2.75; 95% CI: 1.23-6.17; p = 0.014 < 0.05) and smoking (OR: 9.17; 95% CI: 1.69-49.62; p = 0.010 < 0.05) were also significantly associated with placenta accreta. CONCLUSION: Increased first trimester serum PIGF was significantly positively associated with placenta accreta, suggesting that the potential role of PIGF in identifying pregnancies at high risk for placenta accreta. Previous cesarean section history and smoking may be the risk factors for accreta in placenta previa patients.