Buze Chen

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.

PAXIP1-AS1 is associated with immune infiltration and predicts poor prognosis in ovarian cancer

The long non-coding RNA (LncRNA) PAXIP1 antisense RNA 1 (PAXIP1-AS1) was found to promote proliferation, migration, EMT, and apoptosis of ovarian cancer (OC) cells in OC cell lines, but the relationship between PAXIP1-AS1 expression and clinical characteristics, prognosis, and immune infiltration of OC patients and its regulatory network are unclear. 379 OC tissues were collected from The Cancer Genome Atlas (TCGA) database. 427 OC tissues and 88 normal ovarian tissues were collected from GTEx combined TCGA database. 130 OC samples were collected from GSE138866. Kruskal-Wallis test, Wilcoxon sign-rank test, logistic regression, Kaplan-Meier method, Cox regression analysis, Gene set enrichment analysis (GSEA), and immuno-infiltration analysis were used to evaluate the relationship between clinical characteristics and PAXIP1-AS1 expression, prognostic factors, and determine the significant involvement of PAXIP1-AS1 in function. QRT-PCR was used to validate the expression of PAXIP1-AS1 in OC cell lines. Low PAXIP1-AS1 expression in OC was associated with age (P = 0.045), histological grade (P = 0.011), and lymphatic invasion (P = 0.004). Low PAXIP1-AS1 expression predicted a poorer overall survival (OS) (HR: 0.71; 95% CI: 0.55–0.92; P = 0.009), progression free interval (PFS) (HR: 1.776; 95% CI: 1.067–2.955; P = 0.001) and disease specific survival (DSS) (HR: 0.67; 95% CI: 0.51–0.89; P = 0.006). PAXIP1-AS1 expression (HR: 0.711; 95% CI: 0.542–0.934; P = 0.014) was independently correlated with PFS in OC patients. GSEA demonstrated that neutrophil degranulation, signaling by Interleukins, GPCR-ligand binding, G alpha I signaling events, VEGFAVEGFR-2 signaling pathway, naba secreted factors, Class A 1 Rhodopsin-Like Receptors, PI3K-Akt signaling pathway, and Focal Adhesion-PI3K-Akt-mTOR-signaling pathway were differentially enriched in PAXIP1-AS1 high expression phenotype. PAXIP1-AS1 was significantly downregulated in OC cell lines compared with IOSE29 cell line. The expression of PAXIP1-AS1 was associated with immune infiltration. low expression of PAXIP1-AS1 was correlated with poor OS (HR: 0.52; 95% CI: 0.34–0.80; P = 0.003) from GSE138866. There were some genomic variations between the PAXIP1-AS1 high and low expression groups. Low expression of PAXIP1-AS1 was significantly associated with poor survival and immune infiltration in OC. PAXIP1-AS1 could be a promising prognosis biomarker and response to immunotherapy for OC.

MiR-585-3p suppresses tumor proliferation and migration by directly targeting CAPN9 in high grade serous ovarian cancer

Abstract Background Aberrant expression of microRNAs (miRNAs) contributes to the development of high grade serous ovarian cancer (HGSOC). However, the molecular mechanism by which miRNA-585-3p mediates high-grade serous ovarian carcinogenesis is unclear. This study aims to investigate the specific mechanism of action of miR-585-3p in HGSOC. Methods Expression of miR-585-3p in HGSOC tissues and cell lines was detected by qRT-PCR. Cell viability and migration were detected using MTT and transwell system. The expression of target genes and target proteins of miR-585-3p was detected by dual luciferase reporter assay and western blot. Results The expression of miR-585-3p was significantly lower in HGSOC tissues and cells than in normal ovarian tissues and cell lines. In HGSOC tissues, CAPN9 expression was inversely correlated with miR-585-3p expression. MiR-585-3p inhibited the proliferation and migration of HGSOC cells. MiR-585-3p bound to the 3'-untranslated region (UTR) of CAPN9 and inhibits CAPN9 expression. Overexpression of CAPN9 reduced the inhibitory effect of miR-585-3p in HGSOC cells. Conclusions miR-585-3p is significantly down-regulated in HGSOC tissues and cell lines. MiR-585-3p inhibits the proliferation and migration of HGSOC cells by targeting CAPN9.

Molecular Analysis of Prognosis and Immune Infiltration of Ovarian Cancer Based on Homeobox D Genes

Background. Homeobox D (HOXD) genes were associated with cancer pathogenesis. However, the role of HOXD genes in ovarian cancer (OC) and the possible mechanisms involved are unclear. In this study, we analyzed the function and regulatory mechanisms and functions of HOXD genes in OC based on comprehensive bioinformatics analysis. Methods. Expression of HOXD1/3/4/8/9/10/11/12/13 mRNA was analyzed between OC tissue and normal tissue using ONCOMINE, GEO, and TCGA databases. The relationship between HOXD expression and clinical stage was studied by GEPIA. The Kaplan-Meier plotter was used to analyze prognosis. cBioPortal was used to analyze the mutation and coexpression of HOXDs. GO and KEGG analyses were performed by the DAVID software to predict the function of HOXD coexpression genes. Immune infiltration analysis was used to evaluate the relationship between the expression of HOXD genes and 24 immune infiltrating cells. Results. The expression of HOXD3/4/8/9/10/11 was significantly lower in OC tissues than in normal ovarian tissues, while the expression of HOXD1/12/13 was significantly higher in OC tissues. The expression of HOXD genes was associated with FIGO stage, primary therapy outcome, tumor status, anatomic neoplasm subdivision, and age. The expression levels of HOXD1/3/4/8/9/10 correlated with tumor stage. HOXD1/8/9 could be served as ideal biomarkers to distinguish OC from normal tissue. Low HOXD9 expression was associated with shorter overall survival (OS) (HR: 0.75; 95% CI: 0.58–0.98; P = 0.034 ) and progression-free survival (PFS) (HR: 0.69; 95% CI: 0.54–0.87; P = 0.002 ). The HOXD coexpression genes were associated with pathways including cell cycle, TGF-beta signaling pathway, cellular senescence, and Hippo signaling pathway. HOXD genes were significantly associated with immune infiltration. Conclusion. The expression of HOXD genes is associated with clinical characteristics. HOXD9 is a new biomarker of prognosis in OC, and HOXD1/4/8/9/10 may be potential therapeutic targets. The members of the HOXD genes may be the response to immunotherapy for OC.