: Background: Rho GTPase-activating protein 40 (ARHGAP40), downregulated in various tumors, including basal cell carcinoma, has an unclear role in colorectal cancer (CRC). This study aimed to elucidate the function and clinical significance of ARHGAP40 in CRC. Methods: ARHGAP40 expression in CRC tissues was evaluated by immunohistochemistry and analyzed in relation to clinicopathological features and patient survival. Gain-and loss-of-function experiments were performed in CRC cell lines to assess cell proliferation, apoptosis, migration, and invasion. RNA sequencing, co-immunoprecipitation, Ras homolog gene family member A (RhoA) activation assays, and rescue experiments were conducted to explore the underlying mechanism. Results: ARHGAP40 expression was significantly decreased in CRC tissues and cell lines. Low ARHGAP40 expression was associated with poor differentiation ( p < 0.001), deeper tumor invasion ( p = 0.004), lymph node metastasis ( p < 0.001), advanced TNM stage ( p < 0.001), and unfavorable prognosis in patients with CRC ( p < 0.05). Functional experiments showed that ARHGAP40 overexpression suppressed CRC cell proliferation, migration, and invasion, while promoting apoptosis, whereas ARHGAP40 knockdown exerted opposite effects. Mechanistically, ARHGAP40 interacted with RhoA and negatively regulated its activation. Moreover, restoration of RhoA activity partially reversed the effects of ARHGAP40 overexpression on CRC cell proliferation and apoptosis. Conclusions: ARHGAP40 is downregulated in CRC, and its loss may contribute to tumor progression, possibly through dysregulation of RhoA activity.
Bin Lian, Na You, Jing-Yun Wang et al.· Biocell (Mendoza)· 0 citations
Ubiquitin-conjugating enzyme E2A (UBE2A), a member of the ubiquitin-conjugating E2 enzyme family, has been implicated in tumor development; however, its role across human cancer types remains incompletely understood. The present study aimed to systematically characterize the expression pattern, prognostic importance and immune relevance of UBE2A in a pan-cancer context. Public datasets, including The Cancer Genome Atlas, Gene Expression Omnibus and Genotype-Tissue Expression, were integrated to evaluate UBE2A expression, clinical importance, molecular characteristics, immune associations and biological functions across cancer types. Single-cell RNA sequencing data were analyzed to investigate the cellular distribution of UBE2A. Functional validation was performed through UBE2A knockdown in breast cancer cell lines. Results indicated that UBE2A was significantly upregulated in a number of cancer types and was associated with unfavorable overall and progression-free survival. UBE2A expression exhibited significant correlations with immune cell infiltration and immune checkpoint-associated genes across cancer types. Functional enrichment analyses indicated that UBE2A was primarily involved in cell cycle regulation and proliferative processes. Single-cell analysis revealed preferential UBE2A expression in proliferative T-cell populations. Furthermore, in vitro experiments demonstrated that UBE2A knockdown significantly suppressed breast cancer cell proliferation, migration and invasion. Overall, UBE2A was shown to be a promising prognostic biomarker associated with tumor progression, cell cycle activity and immune-associated characteristics across cancer types. Its preferential expression in proliferative T-cell populations and oncogenic role in breast cancer suggest that UBE2A may serve as a potential therapeutic target and a candidate biomarker for evaluating tumor prognosis and the tumor immune microenvironment.
Yunjie Wen, Pengfei Luo· Molecular Medicine Reports· 0 citations
