Atiye Seda Yar Saglam

Diagnostic and prognostic potential of microRNA profiles in endometrioid endometrial cancer

Gene regulation is influenced by microRNAs (miRNAs), a class of non-coding RNAs currently being studied as biomarkers for various diseases. miRNAs, which act as regulators of gene expression and potential biomarkers, were profiled in endometrioid type endometrial cancer (EEC). 28 miRNAs were selected based on their role in regulating EEC-related oncogenes and tumor suppressors (e.g., PTEN, KRAS, β-CATENIN), maintaining tissue stability, and their previous associations with endometrial cancer. This study investigated the expression of miRNAs and their association with key signalling pathways (PI3K/AKT, RAS/MAPK, Wnt/β-Catenin) and their potential as diagnostic biomarkers for EEC. The study also investigated the relationship between miRNA regulation, endometrial pathology, and PTEN, KRAS, and β-CATENIN mRNA expression levels. Women who had received an EEC diagnosis participated in a 14-month prospective cohort study at Gazi University Hospital. Samples were obtained from patients with EEC during frozen sections and healthy women who underwent hysterectomy for benign disease. qPCR examined the miRNA and mRNA levels. 97 women participated, comprising 47 EEC patients and 50 healthy controls. The association was identified between miRNA expression levels and cancer grade. As the tumor grade increases, the expression of miRNAs (miR-let-7c, miR-18a-3p, miR-21, miR-30b, miR-96, miR-130a, miR-141, miR-181b, miR-182, miR-183, miR-2001, miR-200b, miR-200c, miR-203, miR-205, and miR-429) gradually increases. Conversely, twelve miRNAs demonstrated relative expression during the transition from normal endometrium (NE) to EEC (miR-let-7c, miR-let-7e, miR-30c, miR-101, miR-125b, miR-126, miR-129-2, miR-217, miR-324-3p, miR-518b, miR-543, and miR-596). miRNAs could serve as valuable biomarkers for both early detection of EEC and for distinguishing between different tumor grades. We showed that miRNAs have good diagnostic sensitivity for identifying EEC and EC grading. In addition, miRNA improved the ability to discriminate between ECs of different grades.

Hydrogen Sulfide Treatment Enhanced Paclitaxel's Anticancer Effect on the ID8 Murine Epithelial Ovarian Cancer Cell Line

ABSTRACT Background Paclitaxel is a potent agent against ovarian cancer. Hydrogen sulfide (H 2 S) is of particular interest in cancer treatment research. It is known that H 2 S has apoptotic and antiproliferative effects. Objectives We aimed to examine the potential effects of H 2 S donor NaHS and paclitaxel, both individually and when co‐administered, on the ID8 murine epithelial ovarian cancer cell line. Methods We examined the effects of the co‐administration of paclitaxel and NaHS on cell viability, cytotoxicity, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), apoptosis, and proliferation in the ID8 ovarian cancer cell line. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and lactate dehydrogenase tests were performed to ascertain the effect of NaHS and paclitaxel on cell viability and cytotoxicity. Caspase 3/7 levels were quantified in order to detect whether apoptosis is caspase dependent. Quantitative real‐time polymerase chain reaction (qPCR) method was used to ascertain relative mRNA levels of Bcl‐2, Bcl‐xL, Bax, and Bak genes. Results The viability of ID‐8 cells showed a significant reduction following the co‐administration of paclitaxel and NaHS, compared to the paclitaxel administration only. The results of qPCR analysis demonstrated significant alterations in the Bcl‐2, Bcl‐xL, Bax, Bak, Casp3, Casp8, and Casp9 genes' mRNA levels following cotreatment. In contrast to paclitaxel alone, its co‐administration with NaHS resulted in increased apoptosis and decreased ROS levels. The presence of NaHS has been observed to enhance the apoptotic impact of paclitaxel by amplifying the decline in MMP. Conclusion These data indicate that co‐administration of H 2 S with paclitaxel could be useful as a potential agent in the treatment of ovarian cancer. We found that the presence of H 2 S enhanced the antitumor efficacy of paclitaxel.