Insights into sequence characteristics and evolutionary history of DGATs in arthropods.

Triacylglycerol (TAG) is crucial in animal energy storage and membrane biogenesis. The conversion of diacylglycerol (DAG) to triacylglycerol (TAG) is catalyzed by diacylglycerol acyltransferase enzymes (DGATs), which are encoded by genes belonging to two distinct gene families. Although arthropods are known to possess DGATs activities and utilize the glycerol-3-phosphate pathway and MAG pathway for TAG biosynthesis, the sequence characterization and evolutionary history of DGATs in arthropods remains unclear. This study aimed to comparatively evaluate genomic analyses of DGATs in 13 arthropod species and 14 outgroup species. We found that arthropods lack SOAT2 genes within the DGAT1 family, while DGAT2, MOGAT3, AWAT1, and AWAT2 were absent from in DGAT2 family. Gene structure and phylogenetic analyses revealed that DGAT1 and DGAT2 genes come from different gene families. The expression patterns of these genes were further analyzed in crustaceans, demonstrating the importance of DGAT1 in TAG biosynthesis. Additionally, we identified the DGAT1 gene in Swimming crab (P. trituberculatus) undergoes a mutually exclusive alternative splicing event in the molt stages. Our newly determined DGAT inventory data provide a more complete scenario and insights into the evolutionary dynamics and functional diversification of DGATs in arthropods.

A Pyroptosis-Related Gene Panel for Predicting the Prognosis and Immune Microenvironment of Cervical Cancer.

Cervical cancer (CC) is one of the most common malignant tumors of the female reproductive system. And the immune system disorder in patients results in an increasing incidence rate and mortality rate. Pyroptosis is an immune system-related programmed cell death pathway that produces systemic inflammation by releasing pro-inflammatory intracellular components. However, the diagnostic significance of pyroptosis-related genes (PRGs) in CC is still unclear. Therefore, we identified 52 PRGs from the TCGA database and screened three Differentially Expressed Pyroptosis-Related Genes (DEPRGs) in the prognosis of cervical cancer: CHMP4C, GZMB, TNF. The least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate COX regression analysis were then used to construct a gene panel based on the three prognostic DEPRGs. The patients were divided into high-and low-risk groups based on the median risk score of the panel. According to the Kaplan-Meier curve, there was a substantial difference in survival rates between the two groups, with the high-risk group's survival rate being significantly lower than the low-risk group's. The PCA and t-SNE analyses revealed that the panel was able to differentiate patients into high-and low-risk groups. The area under the ROC curve (AUC) shows that the prognostic panel has high sensitivity and specificity. The risk score could then be employed as an independent prognostic factor using univariate and multivariate COX regression analyses paired with clinical data. The analyses of GO and KEGG functional enrichment of differentially expressed genes (DEGs) in the high-and low-risk groups revealed that these genes were primarily engaged in immune response and inflammatory cell chemotaxis. To illustrate immune cell infiltration in CC patients further, we used ssGSEA to compare immune-related cells and immune pathway activation between the high-and low-risk groups. The link between three prognostic DEPRGs and immune-related cells was still being discussed after evaluating immune cell infiltration in the TCGA cohort with "CIBERSORT." In addition, the GEPIA database and qRT-PCR analysis were used to verify the expression levels of prognostic DEPRGs. In conclusion, PRGs are critical in tumor immunity and can be utilized to predict the prognosis of CC.

EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression.

BACKGROUND: Circular RNAs (circRNAs) are noncoding RNAs with stable structures with high expression and tissue-specific expression. Studies have shown that circRNA dysregulation is closely related to the progression of tumours. However, the function and regulatory mechanism of most circRNAs in cervical cancer are still unclear.   METHODS: CircRNAs related to cervical cancer were screened through the Gene Expression Omnibus (GEO) database. qRT-PCR was used to verify the expression of circ_0087429 in cervical cancer tissues and cells. Then, in vivo and in vitro experiments were conducted to evaluate the role of circ_0087429 in the progression of cervical cancer. The role of the circ_0087429/miR-5003-3p/osteoglycin (OGN) axis in the epithelial to mesenchymal transition (EMT) was confirmed by rescue experiments, fluorescence in situ hybridization, luciferase reporter assays, immunofluorescence staining and western blotting. The inhibitory effect of Eukaryotic initiation factor 4A-III (EIF4A3) on the biogenesis of circ_0087429 was verified by RNA immunoprecipitation (RIP) assays and qRT-PCR. RESULTS: circ_0087429 is significantly downregulated in cervical cancer tissues and cells and negatively correlated with International Federation of Gynecology and Obstetrics (FIGO) staging and lymphatic metastasis in cervical cancer patients. circ_0087429 can significantly inhibit the proliferation, migration, invasion and angiogenesis of cervical cancer in vitro and tumour growth and metastasis in vivo. OGN is significantly downregulated in cervical cancer tissues and cells. circ_0087429 can upregulate the expression of OGN by competitively binding with miR-5003-3p, thereby reversing EMT and inhibiting the progression of cervical cancer. EIF4A3 can inhibit circ_0087429 expression by binding to its flanking regions. CONCLUSIONS: As a tumour suppressor, circ_0087429 regulated by EIF4A3 can reverse EMT and inhibit the progression of cervical cancer through the miR-5003-3p/OGN axis. It is expected to become a potential target for the treatment of cervical cancer.

Overexpressed CMTM6 Improves Prognosis and Associated With Immune Infiltrates of Ovarian Cancer.

Ovarian cancer (OV) is an epithelial malignancy that intrigues people for its high mortality and lack of efficient treatment. Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 6 (CMTM6) can be observed in various cancers, but its part in OV remains little known. Hence, the prognostic value and underlying mechanism of CMTM6 in OV were preliminarily evaluated. Here, we determined that CMTM6 expression was higher than that in normal controls. However, the upregulation of CMTM6 was associated with better prognosis. GSEA results suggested that CMTM6 is involved in the immune-related and metabolism-related pathways. GO/KEGG analysis of CMTM6 coexpressed genes was performed to survey the possible regulatory roles of CMTM6 in OV. Subsequently, CMTM6 expression was positively correlated with the infiltration levels of immune cells and the expression of diverse immune cell marker sets. Importantly, CMTM6 may influence prognosis partially by regulating immune infiltration in OV. Last, copy number variations (CNVs) and DNA methylation might prompt the abnormal CMTM6 expression in OV. In conclusion, CMTM6 can serve as a novel prognostic biomarker in patients with OV.

Clinicalpathologic and Prognostic Significance of CGI-58 in Endometrial Cancer.

Recent studies have reported that CGI-58 played an important role in carcinogenesis and tumoral progression in several cancers. In this study, we investigated the expression and prognostic value of CGI-58 in patients with endometrail cancer. Initially, the expression of CGI-58 was analyzed in 552 cases of endometrial carcinoma from The Cancer Genome Atlas (TCGA). Then, the mRNA level of CGI-58 from 32 normal endometrium and 40 endometrial cancer tissues was determined using real-time PCR. In addition, immunohistochemical staining of CGI-58 was performed in 140 endometrial specimens including 35 normal endometrial tissues, 25 atypical endometrial hyperplasia and 80 endometrial cancers. The expression of CGI-58 was significantly up-regulated in endometrial cancer tissues compared with normal endometrial tissue both in TCGA database and clinical cohorts. Over-expression of CGI-58 was significantly correlated with poor histological differentiation. Furthermore, high levels of CGI-58 expression were significantly associated with shorter overall survival for all analyzed cases. Our findings demonstrate that CGI-58 is up-regulated in endometrial cancer and high CGI-58 expression is a poor prognostic marker for endometrial cancer. CGI-58 may be a potential contributor to endometrial cancer oncogenesis and progression.

Risk Stratification Based on Metastatic Pelvic Lymph Node Status in Stage IIIC1p Cervical Cancer.

PURPOSE: Stage IIIC1 cervical cancer showed heterogeneous in oncologic outcomes with highly variable survival rates. Our objective was to determine the prognostic significance of removed and metastatic pelvic lymph node status and further perform risk stratification in patients with stage IIIC1p cervical cancer. PATIENTS AND METHODS: Patients with stage IIIC1p cervical cancer and undergoing radical hysterectomy with lymphadenectomy in 2008-2018 were retrospectively analyzed. Patients' stage was classified using the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) staging schema. Univariate and multivariable models were used to examine the association between removed and metastatic lymph node status and recurrence-free survival/overall survival. RESULTS: During a median follow-up of 34 months, 73 relapses and 44 deaths were observed among 273 patients with stage IIIC1p cervical cancer. Parametrial involvement and metastatic lymph node ratio (mLNR) were identified as independent predictors for recurrence-free survival. Parametrial involvement and mLNR were independent predictors for overall survival. A stratification system was then created based on parametrial involvement and mLNR. A total of 123 (45.1%), 127 (46.5%) and 23 (8.4%) patients were classified into the low-risk, intermediate-risk, and high-risk groups, with as a 5-year recurrence-free survival of 81.7%, 51.1%, 38%, respectively. Compared to the low-risk group, the intermediate- and high-risk groups had a significantly greater risk of recurrence and death. CONCLUSION: The prognosis of stage IIIC1p patients varied significantly. A risk stratification system based on parametrial involvement and mLNR successfully separated patients into low, intermediate, and high-risk group. Our findings could facilitate the practical use of further stratification in Stage IIIC1p cervical cancer.

Cushing's syndrome secondary to ectopic ACTH secretion from carcinoid tumor within an ovarian mature teratoma: a case report and review of the literature.

A 46-year-old woman with Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion caused by primary ovarian mature teratoma with carcinoid components was presented in our case. The patient manifested sustained hypercortisolemia without circadian rhythm and a lack of suppression of either low-dose dexamethasone suppression test (LDDST) or high-dose dexamethasone suppression test (HDDST). There was no evidence of a pituitary mass or secretion of other hormones. After careful clinical evaluation, no other tumor masses were found. Resection of the ovarian tumors led to sharp reduction of serum ACTH and cortisol concentrations. Immunohistochemistry showed positivity in CgA, Syn, CK, NSE. To the best of our knowledge, there are rare reports of an ACTH-secreting carcinoid components located in an ovarian mature teratoma, and bilateral ovarian mature teratoma makes it rarer.