ArticleJournal of experimental & clinical cancer research : CR2020
MicroRNA-148a-3p inhibits progression of hepatocelluar carcimoma by repressing SMAD2 expression in an Ago2 dependent manner.
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- Bioengineered miR-148a-3p suppresses glycolysis and amino acid homeostasis in hepatocellular carcinoma cells by regulating multiple solute carrier transporters.Liver research (Beijing, China) · 2026Article
- Exploring the Role of Extracellular Vesicles in Pancreatic and Hepatobiliary Cancers: Advances Through Artificial Intelligence.International journal of molecular sciences · 2026Review
- Ethyl Acetate Extract from Wenxia Formula (WFEA) Attenuates Immunosuppression in Lung Cancer by Inhibiting Treg DifferentiationCurrent topics in medicinal chemistry · 2026Article
- Interplay Between MicroRNAs and Breast Cancer Therapies: Personalized Therapeutic Potential for HER2-Low Breast Cancer.Cancers · 2025Review
- Interleukin-17A facilitates tumor progressionWorld journal of gastrointestinal oncology · 2025Article
- METTL3-mediated m6A methylation on lncRNA H19 inhibits intrahepatic cholangiocarcinoma progression through PPARγ downregulation.International journal of biological sciences · 2025Article
- Exosomal miR-6126 as a novel therapeutic target for overcoming resistance of anti-cancer effect in hepatocellular carcinoma.BMC cancer · 2024Article
- MicroRNAs in Hepatocellular Carcinoma Pathogenesis: Insights into Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- A study of microRNAs as new prognostic biomarkers in anal cancer patients.Acta oncologica (Stockholm, Sweden) · 2024Article
- Review
- The Role of TGF-β/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis.International journal of biological sciences · 2024Review
- Targeting Reprogrammed Cancer-Associated Fibroblasts with Engineered Mesenchymal Stem Cell Extracellular Vesicles for Pancreatic Cancer Treatment.Biomaterials research · 2024Article
- Emerging role of MicroRNA-Based theranostics in Hepatocellular Carcinoma.Molecular biology reports · 2023Review
- SMAD Proteins in TGF-β Signalling Pathway in Cancer: Regulatory Mechanisms and Clinical Applications.Diagnostics (Basel, Switzerland) · 2023Review
- An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches.International journal of molecular sciences · 2023Review
- Hsa-microRNA-27b-3p inhibits hepatocellular carcinoma progression by inactivating transforming growth factor-activated kinase-binding protein 3/nuclear factor kappa B signalling.Cellular & molecular biology letters · 2022Article
- Selective Loading and Variations in the miRNA Profile of Extracellular Vesicles from Endothelial-like Cells Cultivated under Normoxia and Hypoxia.International journal of molecular sciences · 2022Article
- Mesenchymal stem cells improve liver fibrosis and protect hepatocytes by promoting microRNA-148a-5p-mediated inhibition of Notch signaling pathway.Stem cell research & therapy · 2022Article
- Hsa_circ_0046523 Mediates an Immunosuppressive Tumor Microenvironment by Regulating MiR-148a-3p/PD-L1 Axis in Pancreatic Cancer.Frontiers in oncology · 2022Article
- Inverse relationship between the level of miRNA 148a-3p and both TGF-β1 and FIB-4 in hepatocellular carcinoma.Biochemistry and biophysics reports · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is one of the most prevalent common cancer worldwide with high mortality. Transforming growth factor-β (TGF-β) signaling pathway was reported dysregulated during liver cancer formation and progression. As a key component of TGF-β signaling, the role of SMAD2 and its regulatory mechanisms in HCC remain unclear.
methodsSMAD2 expression in paired HCC specimens were determined by western blot and immunohistochemistry (IHC). quantitative real-time PCR (qRT-PCR) was used to measure mRNA and microRNA (miRNA) expression level. Cell migration, invasion and proliferation ability were evaluated by transwell, CCK8 and EdU assay. In silico websites were used to manifest overall survival rates of HCC patients or to predict miRNAs targeting SMAD2. Dual luciferase reporter assay and anti-Ago2 immunoprecipitation assay were performed to confirm the binding between SMAD2 mRNA and miRNA-148a-3p (miR-148a). Tumorigenesis and lung metastasis mouse model were used to explore the role of miR-148a in vivo. In situ hybridization (ISH) was conducted to determine the expression of miR-148a in liver tissues.
resultsIn this study, we found that SMAD2 was highly expressed in HCC and elevated SMAD2 expression predicted shorter overall survival (OS) time for HCC patients. SMAD2 promoted mobility and proliferation of HCC cells in vitro. We further revealed that the expression of miR-148a was negatively correlated with SMAD2 and found that miR-148a repressed SMAD2 expression by downregulating its mRNA through binding with Argonaute 2 (Ago2) in HCC. Transwell, CCK8 and animal experiments exhibited miR-148a inhibited metastasis and proliferation of HCC in vitro and in vivo. Moreover, the phenotype changes caused by miR-148a manipulation were recovered by rescuing SMAD2 expression in HCC cells. ISH assay indicated miR-148a was downregulated in HCC and low expression of miR-148a associated with more aggressive clinic features and poor prognosis.
conclusionmiR-148a was identified as a repressor of HCC progression by downregulating SMAD2 in an Ago2 dependent manner.
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