Cervical cancer (CC) remains a major global health burden, ranking as the fourth most prevalent malignancy among women. Recent estimates indicate over 600,000 new diagnoses and 340,000 fatalities in 2024, with disproportionate impacts on resource-limited regions [1]. Histologically, squamous cell carcinoma dominates (80% of cases), contrasting with adenocarcinomas (15–20%), which exhibit divergent molecular pathogenesis [2, 3]. In China alone, 2021 recorded 132,788 incident cases and 49,841 deaths, underscoring its persistent public health challenge [4]. Key risk factors encompass early sexual debut, multiparity, tobacco use, prolonged oral contraceptive intake, and persistent human papillomavirus (HPV) infection [5, 6]. Prognosis starkly correlates with staging: early lesions demonstrate 73–98% 5-year survival, plummeting to 20% in advanced disease [7, 8]. Delayed detection, often linked to irregular screening, exacerbates recurrence risks and mortality [9], emphasizing the imperative for robust early diagnostic protocols.

Tripartite motif-containing 11 (TRIM11), an E3 ubiquitin ligase within the TRIM family, orchestrates ubiquitin-mediated protein turnover and immune modulation [10]. Beyond its canonical role in cellular homeostasis, this multifunctional protein intersects with oncogenesis, genetic disorders, and viral pathogenesis [11, 12, 13]. Emerging evidence implicates TRIM11 in tumor progression through post-translational regulation of critical signaling pathways, positioning it as a potential therapeutic target [10]. Dysregulated TRIM11 activates related signaling pathways, thus affecting the phenotype of tumor cells, and is closely associated with tumor development [14]. In lung cancer, TRIM11 expression is associated with tumor size, tumor node metastasis (TNM) stage, lymph node metastasis, and overall survival (OS) [15]. Therefore, we speculate that TRIM11 is a key gene contributing to tumor development in lung cancer. However, the role of TRIM11 in CC remains unclear.

In this study, we analyzed the expression and prognostic value of TRIM11 in CC and various other cancer types.

In recent years, the average age of onset for CC has gradually decreased, with the incidence of CC showing an increasing trend in younger age groups [16]. The development of CC can be effectively controlled through the early examination and prompt treatment of precancerous lesions [17]. Therefore, identifying novel biomarkers closely related to the development of CC is necessary.

As a pivotal member of the TRIM family, TRIM11 has emerged as a promising diagnostic biomarker across malignancies [18]. Our investigation revealed pronounced TRIM11 overexpression in cervical cancer (CC) tissues, correlating with extended PFS and OS in affected patients. Complementary evidence from Zhang et al. [19] demonstrated elevated TRIM11 expression in SiHa and HeLa CC cell lines, where genetic silencing substantially attenuated cellular proliferation, migration, and invasion—underscoring its therapeutic potential. Mechanistic studies implicate TRIM11 in protein kinase B (AKT) pathway hyperactivation, thereby driving CC progression. This aligns with our observations of concordant TRIM11 upregulation at both transcriptomic (mRNA) and proteomic levels in clinical CC specimens. Notably, while TRIM proteins are recognized for their antiviral roles [20], TRIM11 exhibits paradoxical immunomodulatory functions. Interferons (IFNs), central to antiviral defense and cellular regulation [21], are counterintuitively suppressed by TRIM11 via inhibition of interferon-beta (IFN-$\beta$) production and activity [22]. Our data further delineate a tumor-specific regulatory axis: HPV-positive CC tissues displayed orders-of-magnitude higher TRIM11 expression compared to HPV-infected normal epithelia (p 0.001), whereas no differential expression was detected between HPV-positive and HPV-negative normal tissues. Collectively, these findings posit TRIM11 as a dual-faceted driver of CC pathogenesis, operating through oncogenic AKT signaling and IFN-mediated immune evasion. Based on these findings, we speculate that TRIM11 promotes the development of CC and affects the prognosis. The potential mechanism through which TRIM11 contributes to CC is the negative regulation of IFN.

GSEA showed that TRIM11 was closely related to the TGF-$\beta$, calcium, and MAPK signaling pathways in CC. Recently, TGF-$\beta$ has been identified as a promising therapeutic target for CC. In advanced CC, TGF-$\beta$ enhances metastasis, cancer stem cell viability, drug resistance, and immune evasion, thereby promoting tumor development. Blockade of TGF-$\beta$ can effectively improve treatment efficacy, especially in immunotherapy [23]. Ca²⁺ signaling has been shown to promote the growth, proliferation, and metastasis of CC. Mechanistically, regulating various Ca²⁺ channels, pumps, exchangers, sensors, and activation effectors can affect the concentration of Ca²⁺ both inside and outside the cell [24]. The MAPK signaling pathway plays an important role in physiological activities such as cell proliferation, differentiation, apoptosis, and angiogenesis in mammals. In CC, abnormal activation of the MAPK pathway is closely associated with the proliferative, invasive, and metastatic abilities of CC cells [25].

This investigation corroborates prior findings demonstrating tumor-specific TRIM11 dysregulation across malignancies, with marked expression disparities between neoplastic and matched normal tissues. Accumulating evidence positions TRIM11 as a pan-cancer prognostic modulator, exhibiting tissue-specific oncogenic behaviors: Lung Cancer: elevated TRIM11 levels correlate with advanced TNM staging, tumor dimensions, lymph node involvement, and reduced overall survival [26]. Breast Cancer: TRIM11 upregulation drives unchecked cellular proliferation through cell cycle deregulation [27]. Thyroid Cancer: in anaplastic thyroid carcinoma (ATC), TRIM11 silencing attenuates proliferative/migratory capacities and enhances chemosensitivity [28]. Glioma: high-grade gliomas exhibit TRIM11-driven malignant progression via enhanced invasion and treatment resistance, particularly temozolomide (TMZ) in glioblastoma (GBM) [29]. Hepatocellular Carcinoma (HCC): pathological TRIM11 overexpression sustains HCC aggressiveness, whereas its suppression impedes proliferation and metastatic potential [24]. These collective findings establish TRIM11 as a multifaceted therapeutic target, with mechanistic diversity spanning proliferation modulation, treatment resistance, and metastatic programming. In addition, TRIM11 was found to inhibit the PI3K/AKT signaling pathway in HCC cells. These findings suggest that TRIM11 plays an important role in the progression of HCC and serves as a promising therapeutic target for this disease. In this study, we found that in TCGA-GBMLGG and TRIM11 exhibited HRs 1, suggesting tumor-suppressive properties. Conversely, elevated HRs ($>$1) were observed in TCGA-ACC, TCGA-LAML, TCGA-LUAD, TCGA-LIHC, TCGA-SKCM, TCGA-CESC, and TCGA-THCA, implicating TRIM11 as a risk factor in these malignancies.

However, this study has its limitations: (1) small sample size: the study used limited cervical cancer samples from public datasets and only validated results in four tissue pairs, which may reduce reliability. (2) Lack of mechanism validation: while TRIM11 was linked to key pathways (such as TGF-$\beta$ and MAPK), functional experiments to confirm its role were not performed. (3) HPV subtype analysis missing: TRIM11’s association with high-risk HPV subtypes (e.g., HPV16/18) was not explored. (4) Pan-cancer variability: TRIM11’s prognostic role across 34 cancer types requires deeper validation due to differences in cancer biology. In the following research, we will investigate the functionality of TRIM11 in CC.

TRIM11 is overexpressed in cervical cancer and linked to poor survival, potentially driving progression via pathways like TGF-$\beta$ and MAPK. Its role as a biomarker across cancers highlights broad relevance, but larger studies and mechanistic experiments are needed for validation and therapeutic development.

Data related to this study are available by requesting the corresponding author via e-mail.

GZ, HC, and YT designed the research study. GZ performed the research. HC and YT provided help and advice on the qRT-PCR Western blotting experiments. HC analyzed the data. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The study was conducted in accordance with the Declaration of Helsinki. Formal ethical authorization for this investigation was secured from the Institutional Review Board of Zhuzhou Central Hospital (Ethics Approval Code: 20231046). Prior to enrollment, all eligible individuals provided documented informed consent in accordance with institutional protocols.

This study was financially supported by the Natural Science Foundation of Hunan Province (Grant No.: 2025JJ70023) and Social Investment Project of Zhuzhou City in 2024 (No.: 2024-63).

The authors declare no conflict of interest.