CLCA2 overexpression suppresses epithelial-to-mesenchymal transition in cervical cancer cells through inactivation of ERK/JNK/p38-MAPK signaling pathways.

Cervical cancer is an important malignant tumor threatening the physical and mental health of women in the world. As a new calcium activated chloride channel protein, calcium activated chloride channel (CLCA2) plays an important role in tumorigenesis and development. But its role and exact regulatory mechanism in cervical cancer are still unclear. In our study, we found CLCA2 was significantly decreased in cervical cancer cells, and overexpression of CLCA2 inhibited the proliferation, migration and invasion, and promotes apoptosis of cervical cancer cells, and CLCA2 inhibited EMT (Epithelial-mesenchymal transition) through an p38 / JNK / ERK pathway. The results in vivo were consistent with those in vitro. In conclusion, overexpression of CLCA2 inhibited the progression of cervical cancer in vivo and in vitro. This may provide a theoretical basis for CLCA2 as a new indicator of clinical diagnosis and prognosis of cervical cancer or as a potential target of drug therapy.

Quantitative Proteomics Reveals That a Prognostic Signature of the Endometrium of the Polycystic Ovary Syndrome Women Based on Ferroptosis Proteins.

Objective: We aimed to study the relationship between ferroptosis proteins and reproductive outcomes of infertile patients with PCOS and construct the related prognostic model. Methods: These endometrium samples of the study were collected from 33 women with PCOS and 7 control women with successful pregnancies at the Reproductive Center of Lanzhou University Second Hospital, September 2019 to September 2020. The 40 patients' endometrium was identified the differentially expressed proteins (DEPs) using liquid chromatography tandem mass spectrometry. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Ontology (GO) showed that the DEPs related pathways and functions between PCOS and controls. Subsequently, univariate Cox regression analysis and Lasso regression were used to identifying independent prognostic ferroptosis proteins, which were utilized to establish a prognostic model. Then the performance of the prognostic model was evaluated by receiver operating characteristic curve (ROC) and decision curve analysis (DCA). Then clinical data and prognostic model were used to predict the reproductive outcomes of PCOS patients by constructing the nomograms. Finally, we performed the single sample gene set enrichment analysis (ssGSEA) to explore the correlation between risk scores and immune status. Results: A total of 5331 proteins were identified, 391 proteins were differentially expressed in the PCOS and controls. The KEGG analysis revealed that the ferroptosis pathway was significantly different between PCOS and controls. 5 ferroptosis proteins (GPX4, DPP4, G6PD, PCBP1, and PCBP2) prognostic model (FerSig) was constructed via Cox regression and Lasso regression. Patients were separated into high and low-risk groups according to the FerSig. Kaplan-Meier curve showed that patients in the low-risk group had much better reproductive outcomes than those in the high-risk group. The DCA showed that the risk score was an independent predictive factor for reproductive outcomes. Compared with clinical data, ROC curve analysis indicated the FerSig proteins as a potential diagnostic and prognostic factor in PCOS patients. Functional analysis revealed that the FerSig proteins and immune microenvironment were correlated to the prognosis of PCOS. Conclusion: The prognostic model focused on the FerSig proteins could predict the reproductive outcomes of PCOS patients with decreased endometrial receptivity, and provided theoretical basis for individualized treatment.

Bioinformatic identification of genomic instability-associated lncRNAs signatures for improving the clinical outcome of cervical cancer by a prognostic model.

The research is executed to analyze the connection between genomic instability-associated long non-coding RNAs (lncRNAs) and the prognosis of cervical cancer patients. We set a prognostic model up and explored different risk groups' features. The clinical datasets and gene expression profiles of 307 patients have been downloaded from The Cancer Genome Atlas database. We established a prognostic model that combined somatic mutation profiles and lncRNA expression profiles in a tumor genome and identified 35 genomic instability-associated lncRNAs in cervical cancer as a case study. We then stratified patients into low-risk and high-risk groups and were further checked in multiple independent patient cohorts. Patients were separated into two sets: the testing set and the training set. The prognostic model was built using three genomic instability-associated lncRNAs (AC107464.2, MIR100HG, and AP001527.2). Patients in the training set were divided into the high-risk group with shorter overall survival and the low-risk group with longer overall survival (p < 0.001); in the meantime, similar comparable results were found in the testing set (p = 0.046), whole set (p < 0.001). There are also significant differences in patients with histological grades, FIGO stages, and different ages (p < 0.05). The prognostic model focused on genomic instability-associated lncRNAs could predict the prognosis of cervical cancer patients, paving the way for further research into the function and resource of lncRNAs, as well as a key approach to customizing individual care decision-making.

S100A16 Regulates HeLa Cell through the Phosphatidylinositol 3 Kinase (PI3K)/AKT Signaling Pathway.

BACKGROUND S100 calcium-binding protein A16 (S100A16) is closely related to the onset and progression of tumors. MATERIAL AND METHODS In the research, the mainly purpose was to investigate the effect of S100A16 on the proliferation ability, invasion, and angiogenesis of HeLa cells. An adenoviral vector overexpressing S100A16 (Ad-S100A16) was constructed and transfected into HeLa cells, forming a stable cells line of overexpression. The effect of S100A16 on the proliferative capacity of HeLa cells was evaluated by a Cell Counting Kit-8 (CCK-8) assay. Cell migration capacity was determined by a Transwell migration assay. Changes in matrix metalloproteinase-2 (MMP-2), MMP-9, E-cadherin, and vimentin expression were evaluated by a cell-based immunofluorescence assay. The effect of S100A16 on angiogenesis was verified by knockout experiment. RESULTS Overexpression of S100A16 significantly enhanced the proliferative and migratory capacities of HeLa cells (P<0.05), upregulated expression of matrix MMP-2, MMP-9, vimentin, phosphatidylinositol 3 kinase, and phosphorylated protein kinase B, and downregulated expression of E-cadherin. Vascular endothelial growth factor expression increased, phosphatase and tensin homolog expression decreased, and angiogenesis was positively correlated with S100A16 expression. These effects were largely mediated by the activation of the phosphatidylinositol 3 kinase/protein kinase B pathways. CONCLUSIONS S100A16 could promote the proliferation, migration, and tumor angiogenesis of HeLa cells by regulating the phosphatidylinositol 3 kinase/protein kinase B signaling pathways.