ArticleJournal of experimental & clinical cancer research : CR2024
SEC14L3 knockdown inhibited clear cell renal cell carcinoma proliferation, metastasis and sunitinib resistance through an SEC14L3/RPS3/NFκB positive feedback loop.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- MLN4924 suppresses kidney renal clear cell carcinoma progression through coordinated inhibition of Cullin1 neddylation and PSMB10-associated NF-κB inflammatory signaling.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Ribosomal protein S3: a critical regulator of human disease mechanisms.Bioscience reports · 2026Review
- Triggering SORL1 Expression Restricts ccRCC Progression by Inducing Ubiquitination-Mediated c-Myc Degradation.Cancer science · 2026Article
- RPS3 Aggravates Sepsis-Induced Acute Kidney Injury Through Activating NF-kappaB Mediated Renal Inflammatory Responses.Physiological research · 2026Article
- Article
- Insights into the mechanisms of drug resistance in renal cell carcinoma: from multi-omics perspective.International journal of surgery (London, England) · 2026Article
- CircCCDC66 promotes the progression and EMT of renal cell carcinoma via the miR-1278/HOXA13 axis.Journal of translational medicine · 2026Article
- ECM remodeling-associated immune signatures and hub proteins: predictive markers and therapeutic targets for metastatic gastric cancer.Frontiers in immunology · 2026Article
- Extra-Ribosomal Roles for Ribosomal Proteins and Their Relevance to Tumour Suppression, Carcinogenesis and Cancer Progression.Cancers · 2025Review
- Molecular mechanisms of renal cell carcinoma metastasis and potential targets for therapy.Frontiers in cell and developmental biology · 2025Review
- Combining single-cell analysis and molecular docking techniques to construct a prognostic model for colon adenocarcinoma and uncovering inhibin subunit βb as a novel therapeutic target.Frontiers in immunology · 2024Article
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12 authors.
Funding
Abstract
backgroundClear cell renal cell carcinoma (ccRCC) arises from the renal parenchymal epithelium and is the predominant malignant entity of renal cancer, exhibiting increasing incidence and mortality rates over time. SEC14-like 3 (SEC14L3) has emerged as a compelling target for cancer intervention; nevertheless, the precise clinical implications and molecular underpinnings of SEC14L3 in ccRCC remain elusive.
methodsBy leveraging clinical data and data from the TCGA-ccRCC and GEO datasets, we investigated the association between SEC14L3 expression levels and overall survival rates in ccRCC patients. The biological role and mechanism of SEC14L3 in ccRCC were investigated via in vivo and in vitro experiments. Moreover, siRNA-SEC14L3@PDA@MUC12 nanoparticles (SSPM-NPs) were synthesized and assessed for their therapeutic potential against SEC14L3 through in vivo and in vitro assays.
resultsOur investigation revealed upregulated SEC14L3 expression in ccRCC tissues, and exogenous downregulation of SEC14L3 robustly suppressed the malignant traits of ccRCC cells. Mechanistically, knocking down SEC14L3 facilitated the ubiquitination-mediated degradation of ribosomal protein S3 (RPS3) and augmented IκBα accumulation in ccRCC. This concerted action thwarted the nuclear translocation of P65, thereby abrogating the activation of the nuclear factor kappa B (NFκB) signaling pathway and impeding ccRCC cell proliferation and metastasis. Furthermore, diminished SEC14L3 levels exerted a suppressive effect on NFKB1 expression within the NFκB signaling cascade. NFKB1 functions as a transcriptional regulator capable of binding to the SEC14L3 enhancer and promoter, thereby promoting SEC14L3 expression. Consequently, the inhibition of SEC14L3 expression was further potentiated, thus forming a positive feedback loop. Additionally, we observed that downregulation of SEC14L3 significantly increased the sensitivity of ccRCC cells to sunitinib. The evaluation of SSPM-NPs nanotherapy highlighted its effectiveness in combination with sunitinib for inhibiting ccRCC growth.
conclusionOur findings not only underscore the promise of SEC14L3 as a therapeutic target but also unveil an SEC14L3/RPS3/NFκB positive feedback loop that curtails ccRCC progression. Modulating SEC14L3 expression to engage this positive feedback loop might herald novel avenues for ccRCC treatment.
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