Pan-Cancer Landscape of Interferon-Induced Protein 35 and Its Tumor-Promoting Role in Breast Cancer.

MXRA5 promotes the progression and metastasis of breast cancer via activation of the epithelial-to-mesenchymal transition pathway

Breast cancer remains a primary cause of cancer-associated death globally, largely due to distant metastasis and therapeutic resistance. While matrix remodeling associated 5 (MXRA5) has been implicated in inflammation and fibrosis, its specific biological function and mechanistic role in breast cancer progression remain unclear. Herein, multi-omics analysis and in vitro functional assays were employed to investigate the expression pattern, clinical significance, and biological function of MXRA5 within breast cancer. We observed that MXRA5 was considerably upregulated within breast cancer tissues in comparison with normal controls at both mRNA and protein levels. Crucially, elevated MXRA5 expression exhibited a positive correlation with advanced lymph node metastasis and impaired clinical prognosis, including overall survival, disease-specific survival, and progression-free interval, particularly within the Luminal B and HER2+ subtypes. Functional validation demonstrated that MXRA5 silencing markedly repressed the abilities of BT474 and MDA-MB-361 cells to proliferate, to migrate, and to invade in vitro, and significantly reduced lung metastasis in vivo. Mechanistically, bioinformatics analysis and pharmacological rescue experiments demonstrated that MXRA5 promotes tumor aggressiveness by activating the PI3K/AKT/mTOR signaling axis, which subsequently drives the epithelial-to-mesenchymal transition (EMT) pathway, evidenced by the positive regulation of key EMT transcription factors Snail and Twist, as well as the mesenchymal marker Vimentin. Collectively, these findings identify MXRA5 as a novel oncogenic driver in breast carcinoma and reveal its potential as a valuable prognostic biomarker and therapeutic target for managing metastatic disease.

Effects of high CD93 expression on tumor growth and angiogenesis in gastric adenocarcinoma

Background Gastric cancer remains a major cause of cancer-related mortality worldwide, with tumor recurrence and distant metastasis being primary contributors to poor prognosis; however, the underlying molecular mechanisms are not fully understood. CD93, a type I transmembrane glycoprotein, has been implicated in tumor angiogenesis and metastasis in various solid cancers, yet its role in gastric adenocarcinoma (STAD) requires further elucidation. Methods We analyzed CD93 expression and its prognostic significance in STAD using TCGA and an independent cohort. CD93 was overexpressed or knocked out in SGC-7901 cells, with modulation efficiency confirmed by qRT-PCR and Western blot. Functional assays included CCK-8, colony formation, tube formation, endothelial permeability, and transendothelial invasion. A xenograft model using Ctr and sg-CD93 cells was established to assess tumor growth, with IHC performed for Ki67, CD34, and α-SMA. Results CD93 was significantly upregulated in STAD tissues, and high expression correlated with poor patient survival. CD93 overexpression promoted cancer cell proliferation and enhanced tube formation in HUVECs. Interestingly, it also reduced endothelial monolayer permeability and inhibited transendothelial invasion of gastric cancer cells. Conclusion CD93 facilitates gastric adenocarcinoma progression by promoting tumor cell proliferation and angiogenesis. Its dual role in enhancing tube formation while reducing endothelial permeability suggests a complex mechanism in tumor microenvironment regulation, highlighting its potential as a therapeutic target.

expression in cancer cells and correlates with patient survival in breast, ovarian and gastric cancer

ITGA7 functions as a tumor suppressor and regulates migration and invasion in breast cancer

UBTD1: a prognostic and immune biomarker validated in thyroid cancer and pan-cancer analysis

Background Ubiquitin domain containing 1 (UBTD1), a molecule intimately associated with tumorigenesis and progression, is seen as a possible cancer therapy target. However, its diagnostic value, prognostic significance, and immunomodulatory functions of UBTD1 across cancers and in thyroid carcinoma have not yet been fully elucidated. Methods Based on TCGA and other public database resources, this research carried out an extensive examination of the expression levels, prognostic potential, diagnostic value, epigenetic modifications, methylation status, immune significance, and pathway regulation of UBTD1, to explore its biological function in diverse malignant tumors. In addition, through in vitro experiments such as CCK-8, colony formation, transwell, and oris assays, as well as in vivo models of nude mouse xenografts, we validated the expression and regulatory function of UBTD1 in thyroid cancer. Results The study indicates that the overexpression of UBTD1 is prevalent in many cancers and correlates with poor prognosis. UBTD1 is effective to a moderate or strong degree in identifying cancerous tissues compared to healthy ones, and it serves as an independent prognostic factor in ACC, LIHC, READ, and THCA patients. UBTD1 mutations are prevalent across various malignancies and correlate with patient prognosis. In the majority of malignancies, UBTD1 expression is positively associated with m6A methylation, showing increased methylation in its promoter region. Moreover, experiments demonstrated that UBTD1 overexpression reduces THCA cell proliferation, invasion, and migration, whereas its under expression exhibited the opposite biological effects. Conclusion UBTD1 can be used as a biomarker of important clinical value in pan-cancer. Concurrently, this research clarified the expression and role of UBTD1 in THCA. These findings open new avenues for developing tumor treatments targeting UBTD1.

Transcriptional modulation of the PI3K/AKT/mTOR signaling pathway mediated by HPV16 E5, E6, and E7 oncogene expression in breast cancer

Aim: Breast cancer is the most prevalent malignant tumor among women. Human papillomavirus (HPV) has been detected in breast tumors since the 1990s, and beyond its oncogenic potential, therapy resistance driven by viral immune evasion in non-anogenital tumors, such as oropharyngeal cancers, highlights the need to investigate viral activity in breast tissues. Among high-risk HPV types, HPV16 is one of the most prevalent and exhibits the highest carcinogenic potential. Therefore, this study aimed to evaluate the expression of HPV16 oncogenes E5, E6, and E7 in breast tumors, as well as the modulation of the PI3K/AKT/mTOR signaling pathway associated with viral activity. Methods: A total of 92 breast cancer patients were included after Ethics Committee approval. Clinical data were obtained from medical records. RNA was extracted from formalin-fixed, paraffin-embedded tissues and reverse-transcribed into cDNA. Transcripts of HPV oncogenes (E5, E6, and E7), components of the PI3K/AKT/mTOR pathway, and regulatory genes (EGFR and PTEN) were quantified by RT-qPCR. Gene expression levels were calculated using the ΔCt method. Results: Forty-eight samples met RNA quality criteria and were included in the expression analysis. Among these, 77.08% showed expression of at least one viral oncogene, with E5 being the most frequently expressed. The PI3K/AKT/mTOR pathway was modulated in HPV-positive samples, with increased PI3K expression and decreased mTOR expression. Notably, the high expression of E5—associated with immune evasion—combined with reduced mTOR expression suggests that HPV16 status may influence therapeutic response in breast cancer patients. Conclusions: These findings reinforce the importance of further studies investigating HPV activity in breast tumors to better understand its biological and clinical impact.