Biology direct · 2026
TRIM71 suppresses cervical cancer progression by inhibiting Nectin4-mediated Wnt/β-catenin signaling.
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Liu Tianyu, Chen Jian, Dai Bao, Du Diqiao, Chen Min, Zhao Na, Mai Huaxi, Fan Haolin, Lin Lin, Liang Yanchun, Yao Shuzhong
Аннотация
BACKGROUND: Tripartite motif-containing 71 (TRIM71), an RNA-binding E3 ubiquitin ligase, plays essential roles in malignant progression, but its function in cervical cancer (CC) remains unclear.
METHODS: TRIM71 expression was assessed in CC cell lines and clinical specimens using qRT-PCR, Western blotting, and immunohistochemistry. The clinical significance of TRIM71 was evaluated through correlation analyses and survival models. Functional assays in vitro and xenograft models in vivo were used to determine the biological roles of TRIM71. RNA-sequencing, RIP-sequencing, luciferase reporter assays, actinomycin D decay assays, and co-immunoprecipitation assays were performed to elucidate underlying mechanisms.
RESULTS: TRIM71 expression was significantly reduced in CC cell lines and tumor tissues, and its low expression correlated with aggressive clinicopathologic features and poorer survival, identifying it as an independent prognostic factor. Functionally, TRIM71 overexpression impaired CC cell proliferation, migration, invasion, and cytoskeletal remodeling, whereas TRIM71 loss enhanced these malignant behaviors. In vivo, TRIM71 suppressed tumor growth, lung metastasis, and angiogenesis. Transcriptome analysis and molecular assays showed that TRIM71 inhibited Wnt/β-catenin signaling and Epithelial-mesenchymal transition (EMT). RIP-seq revealed Nectin4 as a direct TRIM71 target. TRIM71 bound the Nectin4 3'-UTR and reduced its mRNA stability without affecting ubiquitination. Rescue experiments demonstrated that Nectin4 was essential for TRIM71-mediated repression of Wnt/β-catenin signaling, as Nectin4 restoration or pathway activation reversed TRIM71's inhibitory effects, whereas Nectin4 silencing or pathway inhibition negated the impact of TRIM71 knockout.
CONCLUSIONS: TRIM71 may function as a tumor suppressor in CC by regulating Nectin4 expression and influencing Wnt/β-catenin signaling, EMT, tumor progression, and angiogenesis.
METHODS: TRIM71 expression was assessed in CC cell lines and clinical specimens using qRT-PCR, Western blotting, and immunohistochemistry. The clinical significance of TRIM71 was evaluated through correlation analyses and survival models. Functional assays in vitro and xenograft models in vivo were used to determine the biological roles of TRIM71. RNA-sequencing, RIP-sequencing, luciferase reporter assays, actinomycin D decay assays, and co-immunoprecipitation assays were performed to elucidate underlying mechanisms.
RESULTS: TRIM71 expression was significantly reduced in CC cell lines and tumor tissues, and its low expression correlated with aggressive clinicopathologic features and poorer survival, identifying it as an independent prognostic factor. Functionally, TRIM71 overexpression impaired CC cell proliferation, migration, invasion, and cytoskeletal remodeling, whereas TRIM71 loss enhanced these malignant behaviors. In vivo, TRIM71 suppressed tumor growth, lung metastasis, and angiogenesis. Transcriptome analysis and molecular assays showed that TRIM71 inhibited Wnt/β-catenin signaling and Epithelial-mesenchymal transition (EMT). RIP-seq revealed Nectin4 as a direct TRIM71 target. TRIM71 bound the Nectin4 3'-UTR and reduced its mRNA stability without affecting ubiquitination. Rescue experiments demonstrated that Nectin4 was essential for TRIM71-mediated repression of Wnt/β-catenin signaling, as Nectin4 restoration or pathway activation reversed TRIM71's inhibitory effects, whereas Nectin4 silencing or pathway inhibition negated the impact of TRIM71 knockout.
CONCLUSIONS: TRIM71 may function as a tumor suppressor in CC by regulating Nectin4 expression and influencing Wnt/β-catenin signaling, EMT, tumor progression, and angiogenesis.