Introduction: Epithelial membrane protein 1 (EMP1), a member of the EMP family, is overexpressed in a large number of tumors and is thought to be a cellular connexin on the cell membrane and is involved in proliferation, invasion, metastasis of tumor cells, and epithelial-mesenchymal transition (EMT). Nevertheless, its biomedical function in ovarian cancer is still unclear. Methods: EMP1 was detected in ovarian cancer cell lines by whole transcriptome resequencing. The mRNA of EMP1 was examined by qRT-PCR. The relationship between expression of EMP1 and clinical classification, metastasis, and shortened survival time in ovarian cancer specimens was analysed by immunohistochemical (IHC). The mechanism of EMP1 enhanced proliferation and invasion of ovarian cancer cells was determined by siRNA interference, colony formation, migration and invasion experiments, and Western blot. Results: EMP1 was up-regulated in ovarian cancer cell lines and ovarian cancer tissues in comparison with non-cancerous ovarian specimens. High expression of EMP1 in ovarian cancer specimens was obviously related to high clinical classification, metastasis, and shortened survival time. High expressed EMP1 facilitates cell proliferation, invasion and EMT in ovarian cancer cells. Over-expressed EMP1 increased the protein levels of RAS/ RAF/MAPK/c-JUN. Conclusion: Over-expressed EMP1 in ovarian cancer promotes tumor cell proliferation, invasion, and EMT by the MAPK signaling pathway.

The authors describe a method for enhancing the hybridization chain reaction (HCR) by using gold nanoparticles (AuNPs). This can considerably improve the sensitivity of electrochemical immunoassays as demonstrated for the carbohydrate antigen 125 (CA125), a biomarker for ovarian cancer. Compared to previous HCR based assays, the DNA acting as fuel strands were immobilized onto AuNPs, so that dendrimeric like chains were formed on the electrode after HCR. The improved signal is due to the reaction of DNA on the electrode. Specifically, the reaction of the phosphate groups of DNA with molybdate forms redox-active molybdophosphate, and this generates a strong electrochemical current. The immunosensor was prepared by sequential capturing, on the electrode, (a) antibody against CA125, (b) analyte (CA125), and (c) an aptamer against CA125 to form a sandwich structure. The primer on the aptamer sequence initiates HCR by annealing to one strand of DNA on the AuNPs and to another DNA in solution. The increased loading of DNA molecules onto the electrode increases the amount of phosphate groups and subsequently increases the electrical signal. The sensitivity of the assay is found to be significantly improved compared to assays without HCR and when using conventional HCR. The immunosensor was successfully applied to the determination of CA125 in human serum samples. The detection limit (based on an S/N ratio of 3) is 50 μU.mL. This indicates that this signal amplification strategy has a large potential in terms of clinical applications. It may be modified such that it also can be applied to the determination of other analytes for which proper aptamers are available. Graphical abstract Gold nanoparticle (AuNP) enhanced hybridization chain reaction is reported to improve the sensitivity of electrochemical immunosensor. Hybridization chain reaction is carried out by annealing of H1 DNA strand immobilized on AuNP to the sticky end primer sequence of the aptamer and H2 strand to the complementary sequence of H1.

Aims Clinical evidence indicated the activation of endoplasmic reticulum stress (ERS) in pregnant women with preeclampsia (PE), and the regulatory role of melatonin (MT) in ERS. This study aims to explore the possible effect and mechanism of MT on ERS and on the infiltration of trophoblasts in PE. Methods The serum expression levels of MT and GRP78 in pregnant women with PE were measured. The cell proliferation, invasion, migration and apoptosis of trophoblasts were also determined. The trophoblast cell infiltration in placenta tissues was detected in EVOS image system. The expressions of ERS related proteins were measured by RT‐qPCR and western blot. Key results The PE‐serum treatment on HTR‐8/SVneo cells led to activated ERS and suppressed cell biological functions. PE mouse models after MT treatment or 4‐PBA treatment had reduced blood pressure, proteinuria, apoptosis and increased foetus and placenta weight, in addition to enhanced cell infiltration. Conclusions In vivo and in vitro evidence demonstrated MT can simultaneously suppress ERS and ASK1/JNK signal pathway in PE to promote the infiltration of trophoblasts.

Transporter associated with antigen processing 1 (TAP1) is a protein related immune regulation and plays a role in several malignant tumors. However, the effect of TAP1 on immune infiltration, immunotherapy, and metastasis in different cancers has not been reported till date. The cancer genome atlas database, the tumor immune estimation resource database, and the estimation of stromal and immune cells in malignant tumors using expression (ESTIMATE) algorithm were used to determine the correlation between TAP1 expression and the prognosis of a variety of cancers, immune infiltration, immune checkpoint genes, DNA methylation, and neoantigens. Various enrichment analyses were used to study the correlation between TAP1 and key transcription factors using the Kyoto encyclopedia of genes and genomes (KEGG) pathway in ovarian cancer. Immunological methods were used to evaluate the expression of TAP1 protein in ovarian and cervical cancer, and Kaplan–Meier analysis was used to analyze the prognostic value of TAP1. RNA interference (RNAi) was used to verify the effect of TAP1 on ovarian cancer. Compared with normal tissues, cancer tissues showed a significant increase in the expression of TAP1, and TAP1 expression was related to the poor prognosis of cancers such as ovarian cancer. The expression level of TAP1 was correlated with immune checkpoint genes, DNA methylation, tumor mutation burden, microsatellite instability, and neoantigens in various cancers. Our results showed that TAP1 was upregulated in ovarian cancer cell lines and was associated with poor prognosis. Further, we verified the expression of TAP1-related transcription factors (MEF2A and LEF1) and found that TAP1 was closely related to ovarian cancer metastasis in vitro and in vivo. These results indicated that TAP1 could be used as a biomarker for the diagnosis and prognosis of cancer and as a new therapeutic target.

Background: GRHL2 has been shown to function in ovarian carcinogenesis. However, the relationship between GRHL2 and cisplatin (DDP) resistance in serous ovarian cancer (SOC) is not clear. The purpose of this study was to elucidate the function and mechanism of GRHL2 in DDP resistance of SOC. Materials and Methods: Immunohistochemistry (IHC) was utilized to identify GRHL2 protein expression in DDP resistant and sensitive SOC tissues. GRHL2 mRNA and protein levels were identified using quantitative real-time PCR (qRT-PCR) and Western blotting in SKOV3/DDP and SKOV3 cell lines. We conducted loss-and gain-of-function experiments to uncover the consequence of GRHL2 knockdown or overexpression on the sensitivity of ovarian cancer cells to DDP in vitro and in vivo and the underlying mechanism. Results: It was observed that expression of GRHL2 was higher in DDP resistant SOC tissues relative to DDP sensitive SOC tissues. In addition, the increased expression of GRHL2 led to shorter progression-free survival (PFS) and overall survival (OS). Meanwhile, the GRHL2 transcript and protein levels in SKOV3/DDP were also higher than SKOV3. Small hairpin RNA (shRNA)-facilitated GRHL2 gene knockdown considerably heightened the sensitivity of SKOV3/DDP cells to DDP by inhibiting proliferation and promoting apoptosis, while upregulation of GRHL2 significantly reduced the sensitivity of SKOV3 cells to DDP by promoting proliferation and decreasing apoptosis. In addition, GRHL2 promotes DDP resistance of SOC through activation of ERK/MAPK signaling pathways. Conclusion: Our results suggest that GRHL2 up-regulation predicts a poor prognosis and promotes the resistance of SOC to DDP. Therefore, GRHL2 may be a possible treatment target for cisplatin-resistant serous ovarian cancer.