Lu Miao

Role of TPD52 in Endometrial Cancer: Impact on EMT and the PI3K/AKT and ERK/MAPK Signaling

Introduction: Endometrial carcinoma (EC) incidence and mortality continue to rise, and reliable therapeutic targets remain scarce. We aimed to define the oncogenic role and mechanism of tumor protein D52 (TPD52) in EC, focusing on epithelial–mesenchymal transition (EMT) and the PI3K/AKT and ERK/MAPK signaling pathways. Methods: In this study, we assessed the expression levels of TPD52 in EC tissues and benign endometrial tissues using immunohistochemistry. To further investigate the role of TPD52, we performed experiments both in vitro and in vivo. We transfected siRNA and overexpression (OE) plasmids into Ishikawa and HEC-1-A cell lines to knock down (KD) or overexpress TPD52, respectively. We observed the effects of TPD52 knockdown on tumor growth and EMT through in vitro experiments. Results: TPD52 was significantly upregulated in EC tissues compared with those of benign endometrial tissues. Silencing TPD52 significantly inhibited cell proliferation, migration, and invasion, whereas TPD52 overexpression produced the opposite effects. TPD52 facilitates epithelial-mesenchymal transition (EMT). Moreover, TPD52 stimulates the PI3K/AKT and ERK/MAPK signaling pathways. Discussion: These data position TPD52 as a bona fide EC oncoprotein that drives EMT via dual PI3K/AKT–ERK/MAPK signaling. Limitations include the modest patient cohort and the lack of clinical–pathological correlation analyses. Conclusion: TPD52 promotes EC progression through EMT and PI3K/AKT and ERK/MAPK activation, offering a promising therapeutic target whose clinical utility warrants further investigation.

FHL1 Inhibition by miR-1301-3p Promotes Uterine Corpus Endometrial Carcinoma Cell Proliferation and Migration: A Prognostic Insight

Background: The impact of microRNA-1301-3p (miR-1301-3p) on various cancer subtypes is noteworthy. However, its specific role within the framework of uterine corpus endometrial carcinoma (UCEC) is yet to be clearly defined. Objective: The objective of this research was to investigate and clarify the function of miR-1301-3p in relation to UCEC. Methods: Sample data for our study were sourced from The Cancer Genome Atlas (TCGA). Using various statistical techniques, we assessed the potential of miR-1301-3p as a diagnostic and prognostic indicator, as well as its association with clinical characteristics. Additionally, we conducted an analysis of the genes targeted by miR-1301-3p. The expression levels of miR-1301-3p in uterine corpus endometrial carcinoma (UCEC) cell lines were determined by quantitative real-time PCR (qRT-PCR). Cellular viability and migratory capacity were measured using the CCK8 assay and Transwell migration assays, respectively. Moreover, the expression levels of genes and proteins targeted by miR-1301-3p were identified through dual-luciferase reporter gene assays and Western blot analysis. Results: Expression patterns of miR-1301-3p varied across cancer subtypes, which were significantly linked to specific histological classifications, achieving statistical significance (p < 0.001). In UCEC, higher miR-1301-3p levels correlated with reduced overall survival (p = 0.012) and progression-free survival (p = 0.016), and it emerged as an independent prognostic marker for UCEC. A comparative analysis revealed significantly higher miR-1301-3p levels in UCEC cell lines compared to normal endometrial epithelial cells. Four and a half LIM domains 1 (FHL1) exhibited a negative correlation with miR-1301-3p levels within UCEC tissue samples. miR-1301-3p was shown to promote UCEC cell proliferation and migration through its binding to the 3'-untranslated region (UTR) of the FHL1 gene, thereby repressing FHL1 expression. Additionally, augmenting FHL1 levels was observed to counteract the enhancing impact of miR-1301-3p on UCEC cells. Conclusion: miR-1301-3p regulates the proliferation and migration of UCEC cells by interacting with the FHL1 gene. miR-1301-3p may serve as a promising prognostic biomarker in UCEC.

TPD52 as a Potential Prognostic Biomarker and its Correlation with Immune Infiltrates in Uterine Corpus Endometrial Carcinoma: Bioinformatic Analysis and Experimental Verification

Background: Aberrant expression of tumor protein D52 (TPD52) is associated with some tumors. The role of TPD52 in uterine corpus endometrial carcinoma (UCEC) remains uncertain. Objective: We aimed to investigate the involvement of TPD52 in the pathogenesis of UCEC. Methods: We employed bioinformatics analysis and experimental validation in our study. Results: Our findings indicated that elevated TPD52 expression in UCEC was significantly associated with various clinical factors, including clinical stage, race, weight, body mass index (BMI), histological type, histological grade, surgical approach, and age (p < 0.01). Furthermore, high TPD52 expression was a predictor of poorer overall survival (OS), progress-free survival (PFS), and disease-specific survival (DSS) (p = 0.011, p = 0.006, and p = 0.003, respectively). TPD52 exhibited a significant correlation with DSS (HR: 2.500; 95% CI: 1.153-5.419; p = 0.02). TPD52 was involved in GPCR ligand binding and formation of the cornified envelope in UCEC. Moreover, TPD52 expression was found to be associated with immune infiltration, immune checkpoints, tumor mutation burden (TMB)/ microsatellite instability (MSI), and mRNA stemness indices (mRNAsi). The somatic mutation rate of TPD52 in UCEC was 1.9%. A ceRNA network of AC011447.7/miR-1-3p/TPD52 was constructed. There was excessive TPD52 protein expression. The upregulation of TPD52 expression in UCEC cell lines was found to be statistically significant. Conclusion: TPD52 is upregulated in UCEC and may be a useful patent for prognostic biomarkers of UCEC, which may have important value for clinical treatment and supervision of UCEC patients.