Choriocarcinoma is sensitive to chemotherapy. However, drug resistance has become one of the major problems in recent years. Previous studies have shown that many tumors contained a small fraction of cells that exhibited enhanced tumor initiating potential and stem cell-like properties. It is hypothesized that cancer stem cells (CSCs) are organized in a cellular hierarchy. They also have the qualities of selfrenewal, chemoresistance, and so on. The identification of CSCs in choriocarcinoma and the mechanism contributing to their qualities remain largely unknown. This study focused on the role of AhR, a transcription factor abundantly expressed in many different types of cancer, in the regulation of the expansion of choriocarcinoma CSCs and the exact molecular mechanisms. Spheroid cells isolated from choriocarcinoma in serum-free conditions have stem cell-like characteristics. The expression and nuclear translocation of AhR were markedly elevated in spheroid cells. Activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) significantly increased the spheroid-forming efficiency, chemotherapy resistance, and ability to form tumor xenografts of the cells, whereas AhR knockdown, using short hairpin RNA (shRNA), dramatically reduced stem cell properties. Mechanistically, activating the β-catenin pathway might be an essential biological function of AhR during the regulation of the CSC characteristics. This study also identified ABCG2, which plays an important role in CSCs, as a direct target of AhR. Together, these results strongly suggested the participation of AhR in choriocarcinoma carcinogenesis. Targeting AhR may provide a novel therapeutic opportunity for choriocarcinoma. ARTICLE HISTORY

BackgroundMost ovarian cancer patients with poor prognosis and immune microenvironment play a vital role in the progression of ovarian cancer. We aim to develop a tumor-associated macrophage related gene (TAMRGs) prognostic signature that can stratify and predict overall survival for ovarian cancer. MethodsWe acquired single cell and bulk transcriptome raw data of ovarian cancer from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The immune landscape was identi ed in primary and ascites of ovarian cancer. CIBERSORT deconvolution algorithm, Weighted gene co-expression network analysis (WGCNA), univariate cox analysis, LASSO algorithm, and multivariate cox analysis were performed for the identi cation of TAMRG and the development of prognostic signature. ResultsWe identi ed inter-and intra-patient heterogeneity for immune in ltration cells at a single-cell resolution. Tumor in ltration macrophages showed immunosuppressive characteristics with an M2 phenotype. T cell CD4 memory activated, mast cell activated, neutrophils and macrophages M2 were negatively correlated with overall survival, while macrophages M1 was positively correlated. A total of 219 TAMRGs were identi ed and a novel 6-gene signature (TAP1, CD163, VSIG4, IGKV4-1, CD3E, and MS4A7) with superior prognostic independence was established. ConclusionsThe TAMRG-based signature is expected to be a promising target for prognosis and treatment response of ovarian cancer. BackgroundOvarian cancer (OC), accounts for the highest mortality rate among gynecological malignancies, with 13770 estimated new deaths in the United States, 2021(1). More than 70% of cases of OC are diagnosed at advanced stages with ve-year survival rates approximating 48%(2). Despite appropriate surgery and platinum-based chemotherapy, most patients with ovarian cancer relapse and disseminates(3). It is urgent to identify novel clinical biomarkers and develop new therapeutic strategies for ovarian cancer.Recent evidence has unraveled the tumor microenvironment (TME) plays a vital role in the metastasis of ovarian cancer and is considered a possible therapeutic target for ovarian cancer(4). Among solid tumors, TME of epithelial ovarian cancer is unique because the cancer cells are frequently shed from the primary tumor into the peritoneal cavity, build up a sole microenvironment of malignant ascites. The treatment of ovarian cancer targeting the tumor microenvironment is developing rapidly. Targets mainly focusing on

Background Numerous studies have demonstrated that noncoding RNAs are involved in choriocarcinoma (CC). The competing endogenous RNA (ceRNA) network plays an important role in the occurrence and development of carcinoma. However, the involvement of the ceRNA network in CC remains unclear. The current study aimed to investigate the regulatory mechanism of ceRNA in CC. Material/Methods We downloaded the messenger RNAs (mRNAs) expression profiles (GSE20510 and GSE65654) and microRNAs (miRNAs) expression profiles (GSE32346 and GSE130489) from GEO datasets. The limma package of R software was used to identify differentially expressed RNAs (DERNAs). Then, we performed functional annotation of the differentially expressed mRNAs (DEmRNAs). TargetScan, miRDB, miRWalk, and Starbase were used to construct a CC-specific ceRNA network and select key molecules. Results The results identified a total of 177 DEmRNAs and 189 differentially expressed miRNAs (DEmiRNAs) between the trophoblast and CC cell line samples. Ten differentially expressed lncRNAs (DElncRNAs) were obtained based on experimental studies. The DEmRNAs were mainly enriched in cell proliferation, positive regulation of the apoptotic process, and cell death. A total of 10 genes were ascertained as hub genes. Based on DEmRNAs, DEmiRNAs, and DElncRNAs, a CC-specific ceRNA network was established. Five DElncRNAs, 15 DEmiRNAs, and 45 DEmRNAs were identified. In addition, LINC00261, MEG3, MALAT1, H19, and OGFRP1 were identified as 5 key lncRNAs in choriocarcinoma. Conclusions This study provides novel insights into CC mechanisms and identified potential therapeutic targets for CC.

Unlike other members of the VEGF family, the function of VEGF-B in tumor progression remains to be elucidated. Thus, the present study aimed to determine the function of VEGF-B in human choriocarcinoma cells by investigating its detailed effects and molecular mechanisms. VEGF-B and aryl hydrocarbon receptor (AhR) expression were evaluated by reverse transcription-quantitative PCR analysis and western blot analysis in JEG-3 cells and choriocarcinoma stem-like cells (CSLCs) and their proliferation, migration, and invasion after the transfection of short hairpin RNA VEGF-B, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; AhR agonist) treatment or StemRegenin 1 (SR1; AhR antagonist) treatment were examined by cell proliferation assay, wound healing assay and Transwell assay. In addition, luciferase reporter analysis and bioinformatics data mining were used to investigate the association between VEGF-B and AhR. Upregulation of VEGF-B and AhR expression was observed in CSLCs. Following VEGF-B knockdown or SR1 treatment, the proliferative, migratory, and invasive abilities of CSLCs were significantly decreased, contrary to the findings after TCDD treatment. It was also found that AhR enhanced VEGF-B transcriptional activity by binding to the relative promoter region. These observations indicated that VEGF-B may be an oncogene that promotes choriocarcinoma cell migration and invasion targeted by AhR. Therefore, targeting VEGF-B may provide a novel therapeutic opportunity for choriocarcinoma.

BackgroundMost ovarian cancer patients with poor prognosis and immune microenvironment play a vital role in the progression of ovarian cancer. We aim to develop a tumor-associated macrophage related gene (TAMRGs) prognostic signature that can stratify and predict overall survival for ovarian cancer.MethodsWe acquired single cell and bulk transcriptome raw data of ovarian cancer from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The immune landscape was identified in primary and ascites of ovarian cancer. CIBERSORT deconvolution algorithm, Weighted gene co-expression network analysis (WGCNA), univariate cox analysis, LASSO algorithm, and multivariate cox analysis were performed for the identification of TAMRG and the development of prognostic signature.Results We identified inter-and intra-patient heterogeneity for immune infiltration cells at a single-cell resolution. Tumor infiltration macrophages showed immunosuppressive characteristics with an M2 phenotype. T cell CD4 memory activated, mast cell activated, neutrophils and macrophages M2 were negatively correlated with overall survival, while macrophages M1 was positively correlated. A total of 219 TAMRGs were identified and a novel 6-gene signature (TAP1, CD163, VSIG4, IGKV4-1, CD3E, and MS4A7) with superior prognostic independence was established.ConclusionsThe TAMRG-based signature is expected to be a promising target for prognosis and treatment response of ovarian cancer.