Hua Li

The Downregulation of MMP23B Facilitates the Suppression of Vitality and Induction of Apoptosis in Endometrial Cancer Cells

AbstractEndometrial cancer is a malignant tumor that commonly occurs in the female reproductive system and its incidence is still increasing. The mechanism of the development of endometrial cancer has not yet been fully clarified, so we need to continuously study the relevant mechanisms of endometrial cancer and continue to explore its biomarkers in order to discover more precise and effective treatment methods for endometrial cancer. RT-qPCR (Real-Time quantitative Polymerase Chain Reaction) experiments were used to detect the expression level of MMP23B (Matrix Metalloproteinase 23B) in endometrial cancer cells; the clinical data of the TCGA (The Cancer Genome Atlas) database were downloaded, and gene expression profiles were analyzed to investigate the correlation between MMP23B (Matrix Metalloproteinase 23B) and the survival prognosis of endometrial cancer, and functional enrichment analysis was performed on MMP23B (Matrix Metalloproteinase 23B) related genes. After silencing MMP23B (Matrix Metalloproteinase 23B), CCK8 (Cell Counting Kit-8), RT-qPCR (Real-Time quantitative Polymerase Chain Reaction), scratch assay, and transwell assay were used to detect cell viability, levels of apoptotic factors, migration rate, and invasion number of endometrial cancer, respectively. MMP23B (Matrix Metalloproteinase 23B) was highly expressed in endometrial cancer, which is closely related to a poor survival prognosis for endometrial cancer, and may act on endometrial cancer through apoptosis-related functions. The downregulation of MMP23B (Matrix Metalloproteinase 23B) reduced the cell viability of endometrial cancer cells, upregulated the expression levels of CASP3 (Caspase-3), CASP8 (Caspase-8) and CASP9 (Caspase-9) in cells, and inhibited cell migration and invasion.

XPO1‐Mediated EIF1AX Cytoplasmic Relocation Promotes Tumor Migration and Invasion in Endometrial Carcinoma

Dysregulation of eukaryotic translation initiation factor 1A, X‐linked (EIF1AX), has been implicated in the pathogenesis of some cancers. However, the role of EIF1AX in endometrial carcinoma (EC) remains unknown. We investigated the EIF1AX expression in EC patients and assessed its tumorigenesis‐associated function and nucleocytoplasmic transport mechanism in vitro and in vivo. The results indicated that the cytoplasmic EIF1AX expression showed a gradual increase when going from endometrium normal tissue, simple endometrial hyperplasia, complex endometrial hyperplasia, and endometrial atypical hyperplasia to EC, while vice versa for the nuclear EIF1AX expression. In addition, the cytoplasmic EIF1AX expression was positively correlated with histologic type, high International Federation of Gynecology and Obstetrics (FIGO) grade, advanced FIGO stage, deeper infiltration, high Ki67 index, and shorter recurrence‐free survival in EC patients. In vitro, short hairpin RNA‐mediated EIF1AX depletion or SV40NLS‐mediated EIF1AX import into the nucleus in multiple human EC cells potently suppressed cell migration and invasion, epithelial‐mesenchymal transition, and lung metastasis. Moreover, exportin 1 induced the transport of EIF1AX from the nucleus to the cytoplasm that could be inhibited by leptomycin B treatment or the mutation in the EIF1AX location sequence. These results demonstrate that cytoplasmic EIF1AX may play a key role in the incidence and promotion of EC, and thus, targeting EIF1AX or its nucleocytoplasmic transport process may offer an effective new therapeutic approach to EC.

Characterization of cervical microbiota in cervical intraepithelial neoplasia and cervical cancer using low-coverage whole genome sequencing

ABSTRACT This study characterized compositional shifts in cervical microbiota across disease stages from benign conditions through cervical intraepithelial neoplasia (CIN) to cervical cancer (CC) and investigated interactions with high-risk HPV (hr-HPV) infection using species-resolution profiling to identify severity-associated biomarkers. Cervical exfoliated epithelial cells from 50 patients (eight normal/CIN1, 15 CIN2, 19 CIN3, 5 CC) were analyzed using Low-Coverage Whole Genome Sequencing combined with the Ultrasensitive Chromosomal Aneuploidy Detector (UCAD), a technology featuring a two-step normalization framework that systematically converts raw microbial reads into statistically validated abundance deviations. This enables quantitative identification of pathologically relevant microbiota through cohort-wide Z-score benchmarking. Microbial diversity, differential biomarkers, and HPV-microbiota interactions were assessed using Kruskal-Wallis tests, LEfSe, and Random Forest modeling. Results revealed progressive Lactobacillus depletion (e.g., Lactobacillus crispatus : 32.9% in ≤CIN2 vs. 8.8% in CC) and enrichment of pathobionts like Gardnerella and Bacteroides with lesion severity. CC exhibited the highest microbial diversity (Shannon index: CC vs. CIN2, P =0.045), dominated by HPV16 (11.8%), Bacteroides (55.4%), and Porphyromonas (25.2%). LEfSe identified HPV16, HPV35, Parvimonas micra , and Anaerococcus lactolyticus as CC-specific markers, while Random Forest highlighted Mobiluncus curtisii (importance score=2.0) and HPV16 as key discriminators. CC microbiota showed significant Bacteroidetes enrichment (82% at class level) and reduced Firmicutes abundance. These findings suggest carcinogenesis-associated microbial restructuring, marked by Lactobacillus loss, anaerobic proliferation, and HPV16/35 dominance, potentially modulating disease progression. The identified signatures may inform diagnostic development and microbiome-targeted therapies. IMPORTANCE Our study pioneers an LC-WGS/UCAD approach to characterize microbial across the spectrum from benign lesions through precancerous cervical intraepithelial neoplasia to invasive cervical carcinoma. By identifying lesion-specific microbial biomarkers and HPV-associated cofactors, this work advances mechanistic understanding of microbiota-driven oncogenesis and informs future strategies for microbiota-targeted cervical cancer prevention.

Quantitative Time-Dependent Diffusion MRI for Diagnosis and Aggressiveness Assessment of Endometrial Cancer: A Prospective Study

Preoperative differentiation of benign and malignant endometrial lesions, along with the identification of aggressive histological types of endometrial cancer (EC), is crucial for guiding treatment strategies. Time-dependent diffusion magnetic resonance imaging (TDD-MRI), which allows the characterization of tissue microstructure at the cellular level, is not currently applied for endometrial lesions. This study aimed to evaluate TDD-MRI-derived microstructural parameters for noninvasively distinguishing benign and malignant endometrial lesions and predicting aggressive histological types of EC. This prospective study enrolled 177 patients with clinically suspected EC who underwent TDD-MRI between January 2024 and March 2025. The Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion method was used to extract microstructural parameters, including the cell diameter (d), intracellular volume fraction ( A total of 130 women (mean ± standard deviation age: 56 ± 14 years) administered uterine curettage or surgery were included in the final analysis. All microstructural parameters showed significant differences between benign endometrial lesions and EC ( TDD-MRI-derived microstructural parameters demonstrated high performance in differentiating benign from malignant endometrial diseases and identifying aggressive types of EC.