Min Li

The lncRNA TPTEP1 suppresses PI3K/AKT signalling and inhibits ovarian cancer progression by interacting with PTBP1

AbstractThe expression of the long noncoding RNA (lncRNA) TPTE pseudogene 1 (TPTEP1) is significantly downregulated in ovarian cancer (OC). However, the function and mechanism of the lncRNA TPTEP1 in OC have not been identified. To investigate the expression of the lncRNA TPTEP1, we analysed a publicly available dataset and 20 pairs of OC and normal ovarian samples tissue from the First Affiliated Hospital of Anhui Medical University. Functional assays were used to determine the role of the lncRNA TPTEP1 in OC progression. Furthermore, Western blot, FISH, RNA pull‐down, mass spectrometry and RNA immunoprecipitation approaches were used to determine the mechanism by which the lncRNA TPTEP1 affects OC progression. Animal experiments were used to determine the role of the lncRNA TPTEP1 in ovarian tumorigenicity in vivo. The expression of the lncRNA TPTEP1 in OC tissues was significantly lower than that in normal tissues and low expression of the lncRNA TPTEP1 was significantly correlated with advanced FIGO stage and the presence of malignant ascites in OC patients. In vitro and in vivo, regulation of the expression of the lncRNA TPTEP1 caused changes in OC cell proliferation, migration, invasion and apoptosis. Mechanistically, we found that TPTEP1 directly binds to the polypyrimidine tract‐binding protein 1 (PTBP1) protein and inhibits PI3K/AKT signalling. The lncRNA TPTEP1 inhibits PI3K/AKT signalling by directly binding PTBP1, possibly indicating the molecular mechanism underlying its biological function. With further research, these findings may aid in the development of clinically useful strategies for the treatment of OC.

Validating the 2023 FIGO staging system: A nomogram for endometrioid endometrial cancer and adenocarcinoma

AbstractBackgroundTo find the factors impacting overall survival (OS) prognosis in patients with endometrioid endometrial carcinoma (EEC) and adenocarcinoma and to establish a nomogram model to validate the 2023 International Federation of Obstetrics and Gynecology (FIGO) staging system for endometrial cancer.MethodsData were obtained from the Surveillance, Epidemiology, and End Results (SEER) training cohort. An independent validation cohort was obtained from the First Affiliated Hospital of Anhui Medical University between 2008 and 2023. Cox regression analysis identified independent prognostic factors for OS in EEC and adenocarcinoma patients. A nomogram predicting OS was developed and validated utilizing the C‐index, calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). The relationship between the tumor grade and prognosis of EEC and adenocarcinoma was quantified using net reclassification improvement (NRI), propensity score matching (PSM), and Kaplan–Meier curves.ResultsCox regression analysis identified age, race, marital status, tumor grade, tumor stage, tumor size, and chemotherapy as independent prognostic factors for OS. A nomogram for predicting OS was developed based on these factors. The C‐indexes for the OS nomogram was 0.743 and 0.720 for the SEER training set and external validation set, respectively. The area under the ROC (AUC) for the OS nomogram was 0.755, 0.757, and 0.741 for the SEER data subsets and 0.844, 0.719, and 0.743 for the external validation subsets. Calibration plots showed high concordance between the nomogram‐predicted and observed OS. DCA also demonstrated the clinical utility of the OS nomogram. NRI, PSM, and survival analyses revealed that tumor grade was the most important histopathological factor for EEC and adenocarcinoma prognosis.ConclusionSeven independent prognostic variables for the OS of patients with EEC and adenocarcinoma were identified. The established OS nomogram has good predictive ability and clinical utility and validates the 2023 endometrial cancer FIGO staging system.

SOGA1 drives ovarian cancer progression via regulation of GNAI1 and activation of the TNF/NF-κB pathway

Ovarian cancer (OC) poses a significant public health challenge due to its dismal prognosis and low survival rates. However, the mechanism of OC development remains unclear. Transcriptomic data from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases underwent analysis to identify hub programmed cell death (PCD) genes in OC samples compared to normal controls, utilizing weighted gene co-expression network analysis (WGCNA) and Machine learning models. Then, conduct pan-cancer analysis and nomogram on the hub gene Suppressor Of Glucose, Autophagy Associated 1 (SOGA1). The expression levels of the SOGA1 gene were assessed in clinical samples through Reverse Transcription-Quantitative Real-time Polymerase Chain Reaction (RT-qPCR) experiments. Subsequently, Western Blot (WB), Cell Counting Kit-8 (CCK8), Terminal Deoxynucleotidyl Transferase-Mediated dUTP Nick End Labeling (Tunel) wound healing tests, transwell, RNA sequencing, and subcutaneous tumorigenesis in C57BL/6 mice were conducted to investigate the correlation between SOGA1 and OC cell proliferation, invasion, migration, and other functions, as well as the underlying mechanisms. Through integrated bioinformatics analyses, SOGA1 emerged as a hub gene of PCD in OC. Overexpression of SOGA1 correlated with poor prognosis across multiple cancers, including OC, and served as an independent prognostic factor. The developed nomogram, incorporating SOGA1 expression, accurately predicted overall survival (OS) in OC patients. SOGA1 was significantly upregulated in OC tissues, and high expression of SOGA1 was significantly correlated with lymph node metastasis. Both in vitro and in vivo, modulation of SOGA1 expression led to changes in OC cell proliferation, and SOGA1 promoted OC cell invasion, migration and inhibit apoptosis and inhibit apopapoptosis in vitro. Mechanistically, we found that SOGA1 regulates the Guanine Nucleotide-Binding Protein G (I) Subunit Alpha-1 (GNAI1) protein and facilitates TNF-alpha / NFκB signaling. This study has confirmed that SOGA1 can regulate the progression of the disease by influencing the TNF signaling pathway according to regulate GNAI1 expression.

Xiao‐Jie‐An Capsule Alleviates Uterine Fibroids by Modulating Oestrogen–Progesterone Balance and Reducing Inflammatory Response

ABSTRACTUterine fibroids (UF) are benign tumours composed of smooth muscle cells and fibrous connective tissue. UF are common among women aged 30–50 years and often present with symptoms such as anaemia, pelvic pain and bladder dysfunction. Xiao‐Jie‐An Capsule (XJA), a traditional Chinese medicine formula, has been clinically used to treat UF. However, the underlying mechanisms of its efficacy remain unclear. The aim of this study was to determine the therapeutic effect of XJA and related mechanisms in a UF rat model. The experimental results showed that XJA significantly alleviated abnormalities in uterine morphology, tissue structure and purulent discharge in the UF rats. XJA also reduced serum oestrogen and progesterone in UF rats. Moreover, XJA decreased blood pro‐inflammatory factors in UF rats by modulating the TLR4/NF‐κB pathway. Western blotting and immunohistochemistry analyses revealed that XJA decreased the expression of Bcl‐2, PCNA and Ki67 while increasing the expression of Bax, indicating its role in inhibiting cell proliferation and promoting apoptosis. Additionally, XJA exhibited immunomodulation in UF rats. In summary, our study suggests that XJA alleviates UF by multiple targets and mechanisms, such as restoring the oestrogen–progesterone balance, reducing inflammation, inhibiting cell proliferation, inducing apoptosis and regulating immune function.

Exosomal lncRNA USP30‐AS1 activates the Wnt/β‐catenin signaling pathway to promote cervical cancer progression via stabilization of β‐catenin by USP30

AbstractCervical cancer (CC) remains a major cause of cancer‐related mortality among women globally. Long noncoding RNAs (lncRNAs) play crucial regulatory roles in various cancers, including CC. This study investigates the function of a novel lncRNA, USP30 antisense RNA 1 (USP30‐AS1), in CC tumorigenesis. We analyzed USP30‐AS1 expression using RT‐qPCR and conducted in vitro loss‐of‐function assays, as well as in vivo assays, to evaluate the effects of USP30‐AS1 silencing on CC cell growth and migration. Additional mechanistic experiments, including RNA pull‐down, RNA immunoprecipitation (RIP), and co‐immunoprecipitation (Co‐IP) assays, were performed to elucidate the regulatory mechanisms influenced by USP30‐AS1. We discovered that USP30‐AS1 is overexpressed in CC tissues and cells. Silencing USP30‐AS1 significantly reduced cell proliferation, migration, invasion, and tumor growth. Moreover, USP30‐AS1 was found to modulate the expression of ubiquitin‐specific peptidase 30 (USP30) by sponging microRNA‐2467‐3p (miR‐2467‐3p) and recruiting the FUS RNA binding protein (FUS), thereby stabilizing β‐catenin and activating the Wnt/β‐catenin signaling pathway. These findings suggest that USP30‐AS1 enhances CC cell growth and migration through the miR‐2467‐3p/FUS/USP30 axis, highlighting its potential as a biomarker for CC.

Docetaxel-loaded ultrasmall nanostructured lipid carriers for cancer therapy: in vitro and in vivo evaluation

Lack of cancer-targeted delivery of chemotherapeutics is one of the major obstacles for successful cancer therapy. Nanostructured lipid carriers (NLC) have shown great promise in drug-delivery applications since they are highly scalable, biodegradable nanocarriers with high-drug-loading capacity. However, traditional method prepared NLC, the diameter of which range from 80 to 200 nm, is easily blocked and trapped in perivascular regions without further penetration. As a result, ultrasmall NLC with size under 100 nm or lower range are reported to be ideally tumor targeting carrier as it allows for superior tumor accumulation and permeation. Moreover, surface modification of NLC with folic acid (FA) could significantly increase the drug-delivery efficiency through active targeting effect. In our study, an ultrasmall NLC with FA modification (FA-NLC) was prepared to load docetaxel (DTX) for cancer therapy. Our results showed that DTX-loaded FA-NLC comprised of homogeneous particles with size around 30 nm. In addition, it exhibited great colloidal stability, satisfactory drug-loading efficiency, and high biocompatibility in vitro. Meanwhile, in vivo studies indicated that ultrasmall FA-NLC exhibited greater tumor retention and enhanced antitumor effect compared with control.

Building a Delphi‐Informed Transitional Care Programme Guided by the Omaha System for Gynaecologic Oncology Patients

ABSTRACT Objective This study aimed to develop and validate a standardised transitional care programme for postoperative gynaecologic cancer patients utilising the Omaha system framework. Methods A preliminary transitional care programme was constructed through literature review, semi‐structured interviews and multidisciplinary team discussions. The programme was refined via two rounds of Delphi expert consultations involving 17 oncology nursing specialists. Consensus criteria included expert authority coefficient (Cr), Kendall's W test and coefficient of variation (CV). Results The Delphi consultation demonstrated robust expert consensus, with high authority coefficients (Cr: 0.886 in Round 1; 0.906 in Round 2), exceptional participation rates (88.2% and 100% response rates across two rounds) and statistically significant concordance as evidenced by Kendall's W values (0.233–0.358 and 0.326–0.383; all p  < 0.01). All coefficients of variation (CV) metrics fell within acceptable ranges (0.09–0.42 in the initial phase; 0.08–0.27 post‐refinement). Conclusion The Omaha system‐based transitional care programme exhibits strong expert consensus, scientific rigour and clinical applicability, providing a structured approach to improving postoperative recovery in gynaecologic cancer patients. Relevance to Clinical Practice This protocol standardises postoperative care transitions for gynaecologic oncology patients by integrating multidimensional assessments (physiological, psychosocial and health behaviour domains) and family‐centred education. Clinicians can utilise its evidence‐based framework to reduce preventable complications, enhance caregiver preparedness and improve continuity of care between hospital and home settings. Patient or Public Contribution Six postoperative gynaecologic cancer patients and eight family caregivers participated in semi‐structured interviews to identify unmet transitional care needs. Their insights informed the design of intervention components, including self‐management education and psychosocial support strategies. Patients reviewed draft materials for clarity and cultural appropriateness during Delphi Round 2.