Clinical analysis of uterine parameters evaluated by preoperative magnetic resonance imaging in patients treated by hysteroscopic approach with previous cesarean scar defect-related abnormal uterine bleeding: a retrospective cohort study.

Background: As the cesarean delivery rate continues to rise globally, the treatment of previous cesarean scar defects (PCSD) remains challenging. This study aimed to analyze the variables that may influence the clinical cure rate of patients with PCSD-related abnormal uterine bleeding (AUB) as determined by preoperative magnetic resonance imaging (MRI) following hysteroscopic therapy. Methods: Women who underwent hysteroscopic surgery for PCSD-related AUB at the Gynecology Department of Third Xiangya Hospital of Central South University from 2018 to 2022 were recruited to this retrospective cohort investigation. A total of 147 patients were enrolled in this study and underwent follow-up over 6 months. The significance of clinical characteristics linked to the clinical cure rate of AUB was examined by logistic regression. Results: There were 64 clinically cured (43.5%) and 83 non-clinically cured (56.5%) patients in the study. There were no significant differences in the age, menstrual duration, gravidity, parity, number of cesarean sections, time since the previous cesarean section, uterus position, width, depth, and thickness of the remaining muscle layer of the defect by MRI T2-weighted images (T2WI) before hysteroscopic surgery between the 2 groups. MRI T2WI of the myometrial thickness adjacent to the defect [P=0.038, odds ratio (OR) =2.095, 95% confidence interval (CI): 1.047-4.261] and the distance from the defect to the external cervical os (P=0.021, OR =2.254, 95% CI: 1.136-4.540) before hysteroscopic surgery are risk factors for the clinical cure rate. Conclusions: The myometrial thickness adjacent to the defect and the distance from the defect to the external cervical os in preoperative MRI are risk factors for clinical cure rate in patients with PCSD-related AUB after hysteroscopic treatment, which is helpful for evaluating the prognosis of disease.

Investigation of clinical medicine undergraduates' recognition of narrative medicine.

BACKGROUND: Narrative Medicine (NM), a contemporary medical concept proposed in the 21st century, emphasizes the use of narrative as a literary form in medicine. This study aims to explore the understanding about NM and willingness to learn NM among medical students in our hospital. METHODS: A questionnaire survey was conducted among 130 students at Xiangya Medical College of Central South University. RESULTS: The findings revealed that a small percentage of students (3.1%) were familiar with narrative medicine and its training methods. Knowledge about the treatment skills (77.7%) and core content (55.4%) of narrative medicine was limited among the students. Despite this, a majority (63.1%) expressed a lack of interest in further understanding and learning about narrative medicine. Surprisingly, the survey indicated that students possessed a high level of narrative literacy, even without formal training in narrative medicine. Additionally, over half of the surveyed students (61.5%) believed that narrative medicine could benefit their clinical practice. CONCLUSIONS: This study serves as a preliminary basis for the future development of narrative medicine education in China. It highlights the need to prioritize medical humanities education and provide medical students with more opportunities to access information on narrative medicine. By doing so, we can strive to enhance the visibility and promote the integration of narrative medicine into medical humanities education in China.

The miR-1290/OGN axis in ovarian cancer-associated fibroblasts modulates cancer cell proliferation and invasion.

Despite receiving first-line treatment, ovarian cancer patients continue to experience a high rate of recurrence; nearly all women with ovarian cancer develop chemoresistance and succumb to the disease. In this study, cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs) were isolated from tumor-containing and normal omenta, respectively, and the downregulation of osteoglycin (OGN) in CAFs was observed. OGN overexpression in CAFs significantly inhibited ovarian cancer cell viability, DNA synthesis, and cell invasion. OGN overexpression also changed epithelial-mesenchymal transition (EMT) markers and promoted mTOR and Akt phosphorylation in ovarian cancer cells. miR-1290 targeted OGN and inhibited OGN expression. miR-1290 overexpression in CAFs significantly promoted ovarian cancer cell viability, DNA synthesis, and cell invasion. Moreover, miR-1290 overexpression in CAFs also changed EMT markers and promoted mTOR and Akt phosphorylation within ovarian carcinoma cells. Finally, when ovarian cancer cells in a conditioned medium derived from CAFs co-transduced with miR-1290 mimics and OGN-OE were cultured, the effects of miR-1290 overexpression were partially reversed by OGN overexpression. In nude mouse xenograft tumor models, OGN overexpression in CAFs suppressed tumor growth, whereas miR-1290 overexpression in CAFs increased tumor growth. In conclusion, a miRNA/mRNA axis in ovarian cancer CAFs modulating the proliferative and invasive abilities of ovarian cancer cells, possibly via the Akt/mTOR pathway, was demonstrated.

Narrative medicine in clinical internship teaching practice.

Objective: To explore the effect on empathy skills of integrating narrative medicine instruction into clinical internship undergraduate medical education.Methods: One hundred clinical undergraduate students who were transferred to gynecology and obstetrics in 2016 were selected as subjects and divided into two groups. The control group adopted the traditional practice teaching mode, while the experimental group adopted a narrative medicine integrated with traditional teaching mode. The impact of the narrative medicine course was evaluated using the Davis Empathy Scale, and the students' acceptance of the course was investigated using a self-developed questionnaire.Results: After completion of the rotation, the empathy scores of the experimental group were higher than those of the control group (p < 0.05). Students in the experimental group rated the integration of narrative medicine into the internship class highly, and most students thought that the narrative medicine course was of great benefit with respect to the humanistic quality of medical teaching.Conclusion: The application of narrative medicine teaching in the clinical practice teaching of obstetrics and gynecology promoted students to improve their empathy ability.

Comparative analysis of the clinical efficacy and reproductive outcomes of the hysteroscopic tissue removal system (MyoSure) and hysteroscopic electroresection in the treatment of benign intrauterine lesions.

OBJECTIVE: To compare and analyze the clinical efficacy and reproductive outcomes of the hysteroscopic tissue removal system (MyoSure) and hysteroscopic electroresection in the treatment of benign intrauterine lesions in women of reproductive age. METHODS: This is a retrospective study of patients with benign intrauterine lesions treated with MyoSure or hysteroscopic electroresection. The primary outcomes were operative time and resection completeness, and reproductive outcomes were followed up and compared. Secondary outcomes included perioperative adverse events and postoperative adhesions seen during second-look hysteroscopy. Data analysis was performed using χ2 and Fisher tests for qualitative variables and Student t-test for quantitative variables. RESULTS: The operative times of patients with type 0 or I myoma, endometrial polyps, or retained products of conception in the MyoSure group were shorter than those in the electroresection group but were not significantly different for patients with type II myomas. The complete resection rate was lower in the MyoSure group than in the electroresection group. The degree of decrease in the American Fertility Society score of intrauterine adhesion in the MyoSure group was significantly higher (2.90 ± 1.29 points vs 1.31 ± 0.89 points, P = 0.025). The time to pregnancy and the pregnancy rate were higher in the MyoSure group (13.14 ± 7.85 months vs 16.26 ± 8.22 months, P = 0.040; 65.12% vs 54.55%, P = 0.045), but there was no significant difference in the term live birth rate, premature birth rate, or abortion rate between the two groups. CONCLUSION: MyoSure has advantages of a shortened operative time and improvement in reproductive outcomes such as pregnancy rate. However, for type II myomas, MyoSure has limitations, and a comprehensive evaluation before the procedure is required.

Pancancer analysis of SKA1 mutation and its association with the diagnosis and prognosis of human cancers.

This study aims to explore the role of SKA1 in cancer diagnosis and prognosis and to investigate the mechanism by which SKA1 affects the malignant behaviors of ovarian cancer. Herein, we analyzed the oncogenic role of SKA1 at pan-cancer level by multiple informatics databases and verified the analysis by in vitro experiments. As a result, SKA1 was upregulated across cancers and was related to poor clinical outcome and immune infiltration. Specifically, the constructed nomogram showed superior performance in predicting the prognosis of epithelial ovarian cancer patients. Furthermore, the in vitro experiments revealed that silencing SKA1 significantly inhibited the proliferation, migratory ability and enhanced the cisplatin sensitivity of ovarian cancer cells. Therefore, we explored the oncogenic and potential therapeutic role of SKA1 across cancers through multiple bioinformatic analysis and revealed that SKA1 may promote ovarian cancer progression and chemoresistance to cisplatin by activating the AKT-FOXO3a signaling pathway.

A case report of retroperitoneal ectopic pregnancy with lymphatic migration after in vitro fertilization-embryo transfer: an explanation to embryo distant migration.

OBJECTIVE: To present a rare case of retroperitoneal ectopic pregnancy with lymphatic migration after in vitro fertilization-embryo transfer (IVF-ET) and propose the possible explanation for embryonic migration. DESIGN: Illustrative video presentation. Images, videos (educational videos), and title slides were used to introduce the case of a patient with retroperitoneal ectopic pregnancy with lymphatic migration after IVF-ET and provide a potential explanation for embryo distant migration in the patient. This work was approved by the institutional review board. SETTING: University hospital. PATIENT(S): A 32-year-old woman (gravida 2, para 0) with a history of right salpingectomy was admitted to the hospital 40 days after IVF-ET because of ectopic pregnancy for 1 day; the patient had secondary infertility for 6 years. Gynecologic examination indicated anterior 40-day uterus with no tenderness. A preoperative B-mode ultrasound scan showed that the endometrium was 23 mm, and there was no acoustic image of the pregnant sac in the uterine cavity. Magnetic resonance imaging showed that 1 oval signal measuring approximately 30 × 28 × 35 mm was detected at the gap between the aorta anterior to the third lumbar vertebra and inferior vena cava. The inferior vena cava could be seen on the rear right of the gestational sac, and the abdominal aorta could be seen on the rear left. INTERVENTION(S): Retroperitoneal ectopic pregnancy with lymphatic migration after IVF-ET was diagnosed using B-mode ultrasound, MRI, and pathology analysis and was removed laparoscopically. MAIN OUTCOME MEASURE(S): Mechanism analysis of distant ectopic migration in a patient receiving IVF-ET with a history of tubal surgery. RESULT(S): The patient was diagnosed using B-mode ultrasound and MRI and underwent laparoscopic surgery to diagnose and remove the retroperitoneal ectopic pregnancy tissue. Further, the pregnancy lesion was completely removed using an ultrasonic knife. The pathological examination showed that the pregnancy tissue was located inside an enlarged lymph node surrounded by lymphoid tissue, and lymphocyte infiltration was also seen in the endometrial tissue, suggesting that the implanted embryo migrated to the retroperitoneum through the lymphatic channels. The patient successfully conceived through IVF-ET 1 year after the operation, and a full-term neonate was delivered by cesarean section. CONCLUSION(S): This case reinforces that in patients with a history of tubal surgery, whether unilateral or bilateral, clinicians should pay more attention to the possibility of retroperitoneal pregnancy after IVF-ET and to the follow-up of such patients. The pathological examination report provided evidence that lymphatic migration may be the possible mechanism of retroperitoneal ectopic pregnancy or embryonic migration after intrauterine placement.

Multi-Omics Analysis of MCM2 as a Promising Biomarker in Pan-Cancer.

Minichromosome maintenance 2 (MCM2) is a member of the minichromosomal maintenance family of proteins that mainly regulates DNA replication and the cell cycle and is involved in regulating cancer cell proliferation in various cancers. Previous studies have reported that MCM2 plays a pivotal role in cell proliferation and cancer development. However, few articles have systematically reported the pathogenic roles of MCM2 across cancers. Therefore, the present pan-cancer study was conducted. Various computational tools were used to investigate the MCM2 expression level, genetic mutation rate, and regulating mechanism, immune infiltration, tumor diagnosis and prognosis, therapeutic response and drug sensitivity of various cancers. The expression and function of MCM2 were examined by Western blotting and CCK-8 assays. MCM2 was significantly upregulated in almost all cancers and cancer subtypes in The Cancer Genome Atlas and was closely associated with tumor mutation burden, tumor stage, and immune therapy response. Upregulation of MCM2 expression may be correlated with a high level of alterations rate. MCM2 expression was associated with the infiltration of various immune cells and molecules and markedly associated with a poor prognosis. Western blotting and CCK-8 assays revealed that MCM2 expression was significantly upregulated in melanoma cell lines. Our results also suggested that MCM2 promotes cell proliferation in vitro by activating cell proliferation pathways such as the Akt signaling pathways. This study explored the oncogenic role of MCM2 across cancers, provided data on the underlying mechanisms of these cancers for further research and demonstrated that MCM2 may be a promising target for cancer immunotherapy.

Effect of hyteroscopic uterine septum resection on pregnancy outcomes.

OBJECTIVE: To compare the reproductive outcome following hysteroscopic resection versus usual care in nulliparous women with a septate uterus. METHODS: A retrospective cohort study of nulliparous women with a history of uterine septum and had singleton pregnancies at >20 weeks gestation between Jan. 2016 and Dec. 2019 were conducted. Follow-up was performed through medical record reviews and telephone conversations. The primary outcome was preterm birth at<37weeks gestation, and the secondary outcomes include cesarean delivery, malpresentation, preeclampsia, and birth weight<10th percentile for gestational age. Multivariate logistic regressions were performed to evaluate the effect of hysteroscopic resection on primary and secondary outcomes, after controlling for potential confounding factors. RESULTS: Totally 198 women were included in this study, among which 112 women underwent a hysteroscopic resection and 86 women received usual care. Preterm birth incidence (7.1% vs. 18.6%, P = 0.03) and malpresentation (10.7% vs. 23.3%, P = 0.03) was significantly lower in women treated with hysteroscopic resection compared with those received usual care. Multivariate logistic regression indicated that hysteroscopic resection was significantly associated with decreased risks of preterm birth (OR = 0.36, 95% CI: 0.13-0.68; P < 0.01) and malpresentations (OR = 0.47, 95% CI: 0.25-0.71; P < 0.01), after controlling for potential confounding factors. CONCLUSION: Hysteroscopic resection could significantly reduce the risks of preterm birth and malpresentations compared to usual care for nulliparous women with a septate uterus.

Clinical analysis of 2152 cases of abnormal uterine bleeding treated by NovaSure endometrial ablation.

OBJECTIVE: To evaluate the efficiency, postoperative hysterectomy rate, and influencing factors for therapeutic effect of the NovaSure endometrial ablation procedure in abnormal uterine bleeding (AUB). METHODS: We conducted a retrospective cohort study of 2152 patients from the Department of Gynecology at the Third Xiangya Hospital, CSU from October 2010 to December 2018. RESULTS: From the first year to the eighth year after operation, annual effective rate was above 95.24%, and the differences were not statistically significant. There are statistically significant differences between the effective and ineffective groups with regard to age, intrauterine polyps, total length of the uterus, systemic coagulation disorder, and preoperative hemoglobin. A multivariate logistic regression analysis showed that the risk factors associated with systemic coagulation disorders (P = 0.027) and high total uterine length (P = 0.003) affected NovaSure efficacy in the treatment of AUB. By December 2019, the postoperative hysterectomy rate was 1.86% (40/2152) and the complication rate was 1.67% (36/2152). CONCLUSION: NovaSure is a reliable treatment for AUB and serious medical complications because of its simple operation, low amount of bleeding, quick postoperative recovery, and safe and effective short-term and long-term efficacy. However, it should be carefully selected for patients with a total uterus length exceeding 10 cm.

Multiomics profiling of the expression and prognosis of MCMs in endometrial carcinoma.

Minichromosome maintenance (MCM) family members are a group of genes involved in regulating DNA replication and cell division and have been identified as oncogenes in various cancer types. Several experimental studies have suggested that MCMs are dysregulated in endometrial carcinoma (EC). However, the expression pattern, clinical value and functions of different MCMs have yet to be analyzed systematically and comprehensively. We analyzed expression, survival rate, DNA alteration, PPT network, GGI network, functional enrichment cancer hallmarks and drug sensitivity of MCMs in patients with EC based on diverse datasets, including Oncomine, GEPIA, Kaplan-Meier Plotter, HPA, Sangerbox and GSCALite databases. The results indicated that most MCM members were increased in EC and showed a prognostic value in survival analysis, which were considerately well in terms of PFS and OS prognostic prediction. Importantly, functional enrichment, PPI network and GGI network suggested that MCMs interact with proteins related to DNA replication and cell division, which may be the mechanism of MCM promote EC progression. Further data mining illustrated that MCMs have broad DNA hypomethylation levels and high levels of copy number aberrations in tumor tissue samples, which may be the mechanism causing the high expression level of MCMs. Moreover, MCM2 can activate or suppress diverse cancer-related pathways and is implicated in EC drug sensitivity. Taking together, our findings illustrate the expression pattern, clinical value and function of MCMs in EC and imply that MCMs are potential targets for precision therapy and new biomarkers for the prognosis of patients with EC.

The Emerging Role of Non-coding RNAs in Drug Resistance of Ovarian Cancer.

Ovarian cancer is one of the most common gynecological malignancies with highest mortality rate among all gynecological malignant tumors. Advanced ovarian cancer patients can obtain a survival benefit from chemotherapy, including platinum drugs and paclitaxel. In more recent years, the administration of poly-ADP ribose polymerase inhibitor to patients with BRCA mutations has significantly improved the progression-free survival of ovarian cancer patients. Nevertheless, primary drug resistance or the acquisition of drug resistance eventually leads to treatment failure and poor outcomes for ovarian cancer patients. The mechanism underlying drug resistance in ovarian cancer is complex and has not been fully elucidated. Interestingly, different non-coding RNAs (ncRNAs), such as circular RNAs, long non-coding RNAs and microRNAs, play a critical role in the development of ovarian cancer. Accumulating evidence has indicated that ncRNAs have important regulatory roles in ovarian cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically highlight the emerging roles and the regulatory mechanisms by which ncRNAs affect ovarian cancer chemoresistance. Additionally, we suggest that ncRNAs can be considered as potential diagnostic and prognostic biomarkers as well as novel therapeutic targets for ovarian cancer.

Multi-Omics Profiling Identifies Risk Hypoxia-Related Signatures for Ovarian Cancer Prognosis.

Background: Ovarian cancer (OC) has the highest mortality rate among gynecologic malignancy. Hypoxia is a driver of the malignant progression in OC, which results in poor prognosis. We herein aimed to develop a validated model that was based on the hypoxia genes to systematically evaluate its prognosis in tumor immune microenvironment (TIM). Results: We identified 395 hypoxia-immune genes using weighted gene co-expression network analysis (WGCNA). We then established a nine hypoxia-related genes risk model using least absolute shrinkage and selection operator (LASSO) Cox regression, which efficiently distinguished high-risk patients from low-risk ones. We found that high-risk patients were significantly related to poor prognosis. The high-risk group showed unique immunosuppressive microenvironment, lower antigen presentation, and higher levels of inhibitory cytokines. There were also significant differences in somatic copy number alterations (SCNAs) and mutations between the high- and low-risk groups, indicating immune escape in the high-risk group. Tumor immune dysfunction and exclusion (TIDE) and SubMap algorithms showed that low-risk patients are significantly responsive to programmed cell death protein-1 (PD-1) inhibitors. Conclusions: In this study, we highlighted the clinical significance of hypoxia in OC and established a hypoxia-related model for predicting prognosis and providing potential immunotherapy strategies.

Analysis of Autophagy-Related Signatures Identified Two Distinct Subtypes for Evaluating the Tumor Immune Microenvironment and Predicting Prognosis in Ovarian Cancer.

Ovarian cancer (OC) is one of the most lethal gynecologic malignant tumors. The interaction between autophagy and the tumor immune microenvironment has clinical importance. Hence, it is necessary to explore reliable biomarkers associated with autophagy-related genes (ARGs) for risk stratification in OC. Here, we obtained ARGs from the MSigDB database and downloaded the expression profile of OC from TCGA database. The k-means unsupervised clustering method was used for clustering, and two subclasses of OC (cluster A and cluster B) were identified. SsGSEA method was used to quantify the levels of infiltration of 24 subtypes of immune cells. Metascape and GSEA were performed to reveal the differential gene enrichment in signaling pathways and cellular processes of the subtypes. We found that patients in cluster A were significantly associated with higher immune infiltration and immune-associated signaling pathways. Then, we established a risk model by LASSO Cox regression. ROC analysis and Kaplan-Meier analysis were applied for evaluating the efficiency of the risk signature, patients with low-risk got better outcomes than those with high-risk in overall survival. Finally, ULK2 and GABARAPL1 expression was further validated in clinical samples. In conclusion, Our study constructed an autophagy-related prognostic indicator, and identified two promising targets in OC.

Clinical analysis of the MyoSure hysteroscopic tissue removal system of endometrial polyps in women with an intact hymen.

BACKGROUND: To investigate the clinical efficacy of the MyoSure hysteroscopic tissue removal system in the treatment of endometrial and cervical polyps in women with an intact hymen. METHODS: Retrospective analysis was performed on the clinical data of 32 patients treated with the MyoSure hysteroscopic tissue removal system for endometrial and cervical polyps. RESULTS: All the patients successfully completed the procedure. No intraoperative complications, such as cervical trauma, uterine perforation or TURP syndrome, were reported. The surgical time ranged from 5 to 35 min, with an average time of 19.3 min, and the intraoperative blood loss ranged from 2 to 50 ml with an average blood loss of 10.8 ml. After surgery, all patients were shown to have intact hymens. No residual polyp tissues were observed under the microscope, and abnormal uterine bleeding was relieved. CONCLUSIONS: The MyoSure hysteroscopic tissue removal system can be a safe and effective treatment for endometrial and cervical polyps in women with an intact hymen.

Persistence of RNA transcription during DNA replication delays duplication of transcription start sites until G2/M.

As transcription and replication use DNA as substrate, conflicts between transcription and replication can occur, leading to genome instability with direct consequences for human health. To determine how the two processes are coordinated throughout S phase, we characterize both processes together at high resolution. We find that transcription occurs during DNA replication, with transcription start sites (TSSs) not fully replicated along with surrounding regions and remaining under-replicated until late in the cell cycle. TSSs undergo completion of DNA replication specifically when cells enter mitosis, when RNA polymerase II is removed. Intriguingly, G2/M DNA synthesis occurs at high frequency in unperturbed cell culture, but it is not associated with increased DNA damage and is fundamentally separated from mitotic DNA synthesis. TSSs duplicated in G2/M are characterized by a series of specific features, including high levels of antisense transcription, making them difficult to duplicate during S phase.

Lipopolysaccharide Affects the Proliferation and Glucose Metabolism of Cervical Cancer Cells Through the FRA1/MDM2/p53 Pathway.

Previous studies have found that LPS and FRA1 play opposite roles in cervical cancer. In addition, LPS functions by regulating the expression of FRA1 in many disease models, but there is currently no study of their relationship in the energy metabolism of tumor cells. This study, therefore, investigates the effects of LPS on FRA1-mediated glucose metabolism and the possible mechanisms it may have in cervical cancer cells. We constructed FRA1 stable overexpressing/ empty vector cervical cancer cell lines, where glucose consumption, the level of lactic acid production and the expression of energy metabolism related molecules were detected under the stimulation of LPS. At the same time, the changes in proliferation ability of cervical cancer cells were detected. We discovered that LPS promotes glucose consumption, lactic acid production, pentose phosphate bypass, and inhibits aerobic oxidation, by inhibiting the expression of FRA1; and that LPS promotes the growth of cervical cancer cells. Our results indicate that LPS affects the proliferation and glucose metabolism of cervical cancer cells through the FRA1/MDM2/p53 pathway.

Multi-Omics Analysis of the Therapeutic Value of MAL2 Based on Data Mining in Human Cancers.

Recent studies have reported that T-cell differentiation protein 2 (MAL2) is an important regulator in cancers. Here, we downloaded data from multiple databases to analyze MAL2 expression and function in pan-cancers, especially in ovarian cancer (OC). Gene Expression Profiling Interactive Analysis (GEPIA) databases was used to examine MAL2 expression in 13 types of cancer. Kaplan-Meier plotter database was used to analyze the overall survival rate of MAL2 in pan-cancers. The Catalog of Somatic Mutations in Cancer (COSMIC), cBioPortal, and UCSC databases were used to examine MAL2 mutation in human cancers. Metascape, STRING, and GeneMANIA websites were used to explore MAL2 function in OC. Furthermore, ggplot2 package and ROC package were performed to analyze hub gene expression and undertake receiver operating characteristic (ROC) analysis. Drug sensitivity of MAL2 in OC was examined by the GSCALite database. In order to verify the results from databases above, real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting were conducted to detect the expression of MAL2 in OC cells. CRISPR/Cas9 system was used to knockout the MAL2 gene in the OC cell lines HO8910 and OVCAR3, using specific guide RNA targeting the exons of MAL2. Then, we performed proliferation, colony formation, migration, and invasion assays to investigate the impact of MAL2 in OC cell lines in vivo and in vitro. Epithelial-mesenchymal transition (EMT)-associated biomarkers were significantly altered in vitro via western blotting and qRT-PCR. Taken together, we observed that MAL2 was remarkably dysregulated in multiple cancers and was related to patient overall survival (OS), mutation, and drug sensitivity. Furthermore, experimental results showed that MAL2 deletion negatively regulated the proliferation, migration, invasion, and EMT of OC, indicating that MAL2 is a novel oncogene that can activate EMT, significantly promote both the proliferation and migration of OC in vitro and in vivo, and provide new clues for treatment strategies.

Inhibition of AXL enhances chemosensitivity of human ovarian cancer cells to cisplatin via decreasing glycolysis.

Anexelekto (AXL), a member of the TYRO3-AXL-MER (TAM) family of receptor tyrosine kinases (RTK), is overexpressed in varieties of tumor tissues and promotes tumor development by regulating cell proliferation, migration and invasion. In this study, we investigated the role of AXL in regulating glycolysis in human ovarian cancer (OvCa) cells. We showed that the expression of AXL mRNA and protein was significantly higher in OvCa tissue than that in normal ovarian epithelial tissue. In human OvCa cell lines suppression of AXL significantly inhibited cell proliferation, and increased the sensitivity of OvCa cells to cisplatin, which also proved by nude mice tumor formation experiment. KEGG analysis showed that AXL was significantly enriched in the glycolysis pathways of cancer. Changes in AXL expression in OvCa cells affect tumor glycolysis. We demonstrated that the promotion effect of AXL on glycolysis was mediated by phosphorylating the M2 isoform of pyruvate kinase (PKM2) at Y105. AXL expression was significantly higher in cisplatin-resistant OvCa cells A2780/DDP compared with the parental A2780 cells. Inhibition of AXL decreased the level of glycolysis in A2780/DDP cells, and increased the cytotoxicity of cisplatin against A2780/DDP cells, suggesting that AXL-mediated glycolysis was associated with cisplatin resistance in OvCa. In conclusion, this study demonstrates for the first time that AXL is involved in the regulation of the Warburg effect. Our results not only highlight the clinical value of targeting AXL, but also provide theoretical basis for the combination of AXL inhibitor and cisplatin in the treatment of OvCa.

Fra-1 Inhibits Cell Growth and the Warburg Effect in Cervical Cancer Cells via STAT1 Regulation of the p53 Signaling Pathway.

The oncogenesis of cervical cancer is a multi-factor and multi-step process, and major risk factors include oncogene activation with tumor suppressor gene inactivation, viral factors, and immune factors. For example, the human papillomavirus (HPV) has been linked to the occurrence of cervical cancer. At present, the pathogenesis of cervical cancer remains unclear. Fra-1 (Fos-related antigen 1, also known as FOSL1) is a member of the Fos family and an important nuclear transcription factor that regulates normal cell growth, differentiation, and apoptosis. In the present study, we found that Fra-1 inhibited the proliferation of cervical cancer cells while also promoting apoptosis and affecting cell cycle distribution. Moreover, Fra-1 up-regulated STAT1 expression and modulated p53 signal pathway activity in cervical cancer cells. Overexpression of Fra-1 inhibited cell senescence by altering sirtuin 1 (SIRT1) expression in HeLa cells, and Fra-1 overexpression restored mitochondrial disorder and suppressed metabolic reprogramming in HeLa cells. Silencing of STAT1 impaired the inhibitory effect of Fra-1 on cervical cancer cell growth, while knock-down of STAT1 reversed the effect on cell senescence and mitochondrial dysfunction caused by Fra-1 in HeLa cells. Silencing of STAT1 also recovered metabolic reprogramming in cervical cancer cells. In summary, our results show that Fra-1 inhibited cervical cancer cell growth and the Warburg effect via STAT1-mediated regulation of the p53 signaling pathway.