Discovery Medicine

Investigating Anti-Tumor Effects of Irisin in Cervical Cancer Cells: Cell Viability, Migration, and Tumor-Associated Macrophage Polarization

Cervical cancer is a major concern in women's health. Investigating the biological behavior of cancer cells can help to understand the underlying pathogenesis and offer novel insights into disease management. Therefore, this study evaluated the effect of irisin on the biological behaviors of cervical cancer cells and elucidated its underlying mechanism. Cell viability of Caski and HeLa cells under different irisin concentrations was examined using the cell counting kit-8 (CCK-8) assay. Cell proliferation and autophagy levels were assessed at protein and mRNA levels using Western blot (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) analyses, respectively. Apoptosis was determined by assessing the levels of activated caspase-3, caspase-8, and caspase-9 using corresponding enzyme-linked immunosorbent assay (ELISA) kits. The impact of irisin on cell cycle and apoptosis rates was evaluated using flow cytometry analysis. However, the migratory capability of irisin-treated cells was assessed using the scratch healing assay. Furthermore, expression levels of matrix metalloproteinases (MMP2, MMP7, and MMP9) were determined using WB analysis, and the Transwell assay assessed the invasive potential of the cells. The impact of irisin on macrophage polarization was examined through CD86 and CD206 typing using flow cytometry, and macrophage polarization status was determined by detecting the levels of inflammatory cytokines (interleukin (IL)-6, IL-10) and tumor necrosis factor-α (TNF-α). Then, THP-1 cells were directly co-cultured with cervical cancer cells to detect their effect on their biological behavior with or without irisin treatment, aiming to explore the underlying mechanism. Irisin reduces cervical cancer cell viability and decreases the protein and mRNA expression levels of minichromosome maintenance complex component 2 (MCM2), antigen identified by monoclonal antibody Ki67 (Ki67), and proliferating cell nuclear antigen (PCNA) ( Irisin exhibits potent anti-cancer effects on cervical cancer cells by modulating several key cellular processes and altering the tumor microenvironment. Irisin effectively inhibits the proliferation, invasion, and migration of cervical cancer cells and affects the levels of autophagy and apoptosis. Furthermore, it inhibits cancer cells by affecting the polarization of tumor-associated macrophages, underscoring their potential as a novel therapeutic target for treating cervical cancer.

METTL3 Regulates the Translation of Oncogene Myc through m6A Modification and Promotes the Occurrence and Development of Cervical Cancer

Cervical cancer (CC) is one of the major types of gynecological cancer, with a high global incidence and mortality rate. Methyltransferase-like 3 (METTL3), a key constituent of methyltransferase, plays a crucial role in various biological processes. Still, only a rare report has been made on its involvement in the progression of CC. Therefore, this study aims to investigate the impact of METTL3 in CC and its molecular mechanisms. Gene expression datasets about CC were obtained from the Gene Expression Omnibus (GEO) database, and the expression of Analysis of the GEO database indicated elevated expression of METTL3 and Myc in CC tissues. Patients with high METTL3 expression had shorter disease-free survival, and patients with high Myc expression had shorter overall survival. Following the knockdown of

Regulations of Exosomal-Transmitted AFAP1-AS1 LncRNA on Ovarian Cancer Cell Migration and Invasion

Adolescent ovarian cancer (OC) has high malignancy. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of various malignancies, but their role in adolescent OC remains poorly understood. This study aims to assess the modulatory role of Exosome-transmitted lncRNA Actin filament-associated protein 1 Antisense RNA 1 ( We recruited a cohort of 40 adolescent patients diagnosed with OC and a control group of 40 healthy individuals. Serum samples were collected from both groups prior surgical intervention. Exosomes from peripheral blood and ascites were collected via differential centrifugation. The expression levels of Our findings demonstrate that the expression of Our data provide evidence for the oncogenic role of

Twist-1 Stimulates the Malignant Behaviors of Hydatidiform Mole via the PI3K/AKT Pathway

Hydatidiform mole (HM) is a common pregnancy disease among women of gestational age. Twist-related protein 1 (Twist-1) is involved in the development of various tumors, but its role in HM is poorly defined. This study aimed to explore Twist-1 expression and its biological function in HM cells. Twist-1 expression in HM was detected by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). The effects of silencing Twist-1 on choriocarcinoma (CCA) cell proliferation were detected by cell counting kit-8 (CCK-8) and clone formation assays. CCA cell migration and invasion were detected through transwell assay. Western blot was used to detect epithelial-mesenchymal transition (EMT) and the expression of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway-related proteins. Twist-1 expression was upregulated in HM tissues ( Silencing Twist-1 inhibits the malignant behavior of CCA cells, which may play a part by inhibiting the EMT process and the PI3K/AKT pathway.

FOXM1 Contributes to Chemotherapy Sensitivity in Cervical Cancer by Regulating TTK

The emergence of chemotherapy resistance usually causes therapeutic failure in advanced cervical cancer. Forkhead box protein M1 (FOXM1) and threonine tyrosine kinase (TTK) are closely associated with cancer drug sensitivity, but the mechanism of FOXM1 on TTK involvement in chemo-treated cervical cancer remains unclear. Here, we aimed to observe the effects of FOXM1 on TTK and on chemotherapy sensitivity in cervical cancer. The expressions of FOXM1 and TTK in cervical cancer tissues and para-cancerous tissues were analyzed by immunohistochemistry. SiHa and Hela cells were transfected with human lentivirus-FOXM1, small interfering RNA (siRNA) or pcDNA3.1/FOXM1 to analyze the changes in TTK protein expression. Furthermore, the cells were treated with paclitaxel (8 μM) or cisplatin (10 μM) to analyze the effects of FOXM1 on chemotherapy sensitivity. SiHa cells were used to construct a xenograft model to study the effects of FOXM1 expression in response to paclitaxel treatment. The tumor size and weight were observed. The expressions of Ki-67, FOXM1, and TTK protein in tumor tissues were measured by immunohistochemistry. High expression of FOXM1 and TTK were found in the cervical cancer tissues ( FOXM1 regulated TTK and affected the therapeutic efficacy of cisplatin and paclitaxel in cervical cancer.

Downregulation of HS6ST2 Inhibits Cervical Cancer Cell Migration and Invasion in Vivo and in Vitro

Emerging evidence indicates the importance of heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) in a number of developmental processes. Little is known regarding its biological function in regulating cervical cancer (CC) progression. In this study, we aim to explore the role of HS6ST2 in CC progression. The transcriptome sequencing data of CC tissues from three databases, GSE64217, GSE138080, and GSE63514, was examined for genes with significant changes. The expression profile for HS6ST2 within CC tissue was then assessed through fluorescence quantitative PCR and immunohistochemistry and compared to data from patients with clinicopathological features. A multivariate survival analysis was performed using the COX regression. The real-time quantitative PCR assessed the HS6ST2 expression profile within CC cellular cultures. The results of knocking down HS6ST2, considering the proliferative activity and invasiveness of CC cultures HS6ST2 was severely upregulated within CC tissues across the three explored databases (GSE64217, GSE138080, and GSE63514). Fluorescent quantitative PCR and immunohistochemistry experiments identified HS6ST2 as highly upregulated within patients CC tissues. Survival analysis taking into account the parameters of lymph node metastasis, Federation of Gynecology and Obstetrics (FIGO) stage, depth of invasion, pathological grade, and HS6ST2 expression level demonstrated that individuals with downregulated HS6ST2 exhibited considerably extended progression-free survival (PFS) and overall survival (OS) in comparison to upregulated HS6ST2 cases. According to the findings of COX univariate analysis, the parameters lymph node metastasis, FIGO stage, depth of invasion, pathological grade, and HS6ST2 expression level, all showed a statistically significant correlation with effect upon prognosis of CC patients. The FIGO stage, depth of invasion and expression level of HS6ST2 were identified as independent risk variables influencing CC case prognosis within subsequent COX multivariate analysis. Cell function experiments proved that HS6ST2 knockdown can considerably diminish the proliferative potential, stemness and invasive traits of CC cells. Tumor formation experiments in nude mice The clinicopathological features and the survival time of the patients significantly correlate with the level of HS6ST2 expression in CC tissue samples.

Review on Sertoli-Leydig Cell Tumours of the Ovary

Sertoli-Leydig cell tumours (SLCTs) represent a subset of mixed sex cord-stromal tumours (SCSTs), a rare form of non-epithelial ovarian tumours comprising less than 7% of malignant cases. Among other types of SCSTs, SLCTs are one of the more prevalent types observed in young adults. SLCTs are classified into 5 histologic categories based on differentiation levels and histological variants. Diverse chromosomal and genetic mutations have been identified in SLCTs, with the most well-studied being the genetic mutations observed in the Dicer 1, Ribonuclease III (

S100A8 Mediates Autophagy and Apoptosis in Ovarian Cancer Cells via the PI3K/Akt Pathway

Ovarian cancer (OC) is one of the most lethal forms of gynecological malignancies. Previous studies indicate that S100 calcium-binding protein A8 (S100A8) regulation of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway has been implicated in the development and progression of a variety of cancers, but its effects and mechanisms in OC cells remain unclear. This study aims to explore the effect of S100A8 on autophagy and apoptosis in OC cells and the regulatory effects of the PI3K/Akt signaling pathway. Viability of OC cells was assessed by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell migration was determined using the Transwell assay. The effect of S100A8 on autophagy in OC cells was assessed using immunofluorescence and transmission electron microscopy. Flow cytometry analysis was conducted to assess apoptosis. To study the expression of genes associated with cell viability, migration, autophagy, apoptosis, and the PI3K/Akt signaling pathway, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were performed. High concentrations of S100A8 protein significantly inhibited the activity of OC cells, with the most pronounced effect observed at 72 hours ( With its ability to inhibit proliferation, migration, and autophagy, and promote apoptosis in OC cells by inhibiting the PI3K/Akt pathway, S100A8 holds promise as a potential target for the prevention and treatment of OC, providing an effective therapeutic strategy for the clinic.

Role of KIF20A Depletion in Inhibiting Ovarian Cancer Progression: Insights From PTEN and M2 Macrophage Polarization

Recent studies have proven the oncogenic role of kinesin family member 20A ( Ovarian cancer tissues and cells exhibited upregulated

Rare but Still There: A Scoping Review on Endometriosis-Associated Ovarian Cancer

Endometriosis is a medical condition affecting at least up to 10% of women of reproductive age. This condition occurs when ectopic endometrial glands and stroma implant outside the uterus and there are several theories regarding the underlying origins of the disease. Endometriosis is one of the major causes of severe dysmenorrhoea, chronic pelvic pain and infertility. While endometriosis is generally a non-malignant condition, it rarely may transform into an invasive cancer, and increase the risk for epithelial ovarian cancer, notably endometrioid or clear cell ovarian cancer. Despite the increased risk, the mechanisms behind the development of endometriosis-associated ovarian cancer (EAOC) are not yet well understood. Recent investigations have delved into the intricate interplay between endometriosis and EAOC, exploring pathways involving oxidative stress, inflammation, hyperestrogenism, and the discovery of genetic mutations within endometriotic lesions that hint at a transition towards invasive carcinoma. Efforts have been made to identify intermediary lesions between endometriosis and EAOC, which may enable earlier detection of endometriosis at risk of malignant transformation or even prevention of the transformation altogether. However, given the rarity of this malignancy, there is still the risk of late or missed diagnosis, with the risk of inappropriate management being offered to the patient, and the higher risk of poor prognosis and increased morbidity and mortality. This scoping review aims to summarize existing data on EAOC, with a focus on endometrioid and clear cell histologic subtypes. It also provides insights into its identification, prognosis, and delineating management strategies, seeking to provide a holistic understanding of the complexities surrounding EAOC, facilitating further research and the development of more effective prevention and treatment approaches.

The Role of Lymphovascular Space Invasion and Cytology in the Prognosis of Endometrial Cancer

Lymphovascular space invasion (LVSI) and cytology are both independent and strong prognostic factors in endometrial cancer. This study aims to highlight the impact of LVSI and cytology positivity on prognosis, in addition to molecular classification. A retrospective review was conducted on the records of 223 patients with endometrial cancer diagnosed between January 2011 and January 2021. The inclusion criteria stipulated that the patients were diagnosed with endometrial cancer by endometrial biopsy and were operated in the clinic. The exclusion criteria included sarcoma in the postoperative pathology report results or synchronous tumor. Staging was performed according to the Fédération internationale de gynécologie et d'obstétrique (FIGO) 2009 criteria. Cytology (using 50 cc saline) was obtained upon entry into the peritoneal cavity. In 20 patients, saline was not used due to the presence of ascites in the abdomen. The Kaplan-Meier method was employed to evaluate overall survival and progression-free survival. Survival rates were compared in terms of cytology and LVSI. After analyzing the postoperative pathology results, it was found that the mean tumor size was 4.03 ± 2.3 cm. The most common histological type was endometrioid carcinoma, with stage IA being the most common stage. Out of 223 patients with endometrial cancer, the overall survival rate was 82.4%, and the progression-free survival rate was 88.3%. For patients negative for LVSI, the progression-free survival rate was 93%, while for LVSI-positive patients, it was 77.3% ( In our study, we observed that LVSI positivity and cytology positivity also reduced the overall survival rate. We aimed to highlight that, in addition to molecular classification, cytology positivity and LVSI positivity are still highly significant and independent factors in prognosis.

CircRNA Hsa_circ_0120175 Promotes Ovarian Cancer Tumorigenesis and Predicts a Poor Prognosis

Circular RNA is a type of non-coding RNA that is commonly found in eukaryotic genomes. They play an essential role in the biological processes of cell proliferation and cell apoptosis involved in normal development and abnormal tumorigenesis. In this study, we examined whether that the circular RNA GENE A total of 40 patients with ovarian cancer were included in this study, and tissue samples were collected from both ovarian cancer tissues and paracancer tissues. The levels of

Tumor Suppressor LINC02487 Inhibits the Progression of Cervical Cancer in Vitro by Regulating the PTEN/Akt/mTOR Pathway

Cervical cancer (CC) ranks among the most prevalent malignant tumors affecting the female reproductive system. Nonetheless, various shortcomings exist within current treatment approaches for CC. Therefore, the quest for new intervention targets holds significant importance. Research has demonstrated that long non-coding RNA (lncRNA) long intergenic non-protein coding RNA 2487 ( A positive correlation was observed between

Investigating the Spatial Distribution of Proliferating Cells in Primary Ovarian Cancers

Ovarian cancer (OC) accounts for about 4% of female cancers globally. While Ki67-immunopositive (Ki67 A total of 100 tissue cores, included in a tissue microarray (TMA) representing 5 clear cell carcinomas, 62 serous carcinomas, 10 mucinous adenocarcinomas, 3 endometrioid adenocarcinomas, 10 lymph node metastases from OC, and 10 samples of adjacent normal ovary tissue, were stained using a standardized immunohistochemical protocol. The computer-aided image analysis system assessed the 2D distribution pattern of Ki67 Significant differences in Ki67 Cell proliferation is a hallmark of OCs. This study provides new evidence that investigating the Ki67