ArticleBMC cancer2013
MicroRNA-21 promotes hepatocellular carcinoma HepG2 cell proliferation through repression of mitogen-activated protein kinase-kinase 3.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 94 citations in OpenAlex.
- Reexpression of Let-7g microRNA inhibits the proliferation and migration via K-Ras/HMGA2/snail axis in hepatocellular carcinoma.BioMed research international · 2014Trial
- Macrophage polarization and non-coding RNAs in colorectal cancer progression and metastasis.Medical oncology (Northwood, London, England) · 2026Review
- Is cancer the result of uncontrolled cellular growth? a glance into the tumorigenic process.Cancer cell international · 2026Review
- Recent advances in ultrasound-targeted nanobubbles combined with cancer immunotherapy: Mechanisms, applications, and challenges.Fundamental research · 2026Review
- SATB1 in cancer progression and metastasis: mechanisms and therapeutic potential.Frontiers in oncology · 2025Review
- MicroRNA Nobel Prize: Timely Recognition and High Anticipation of Future Products-A Prospective Analysis.International journal of molecular sciences · 2024Review
- Engineering Versatile Nanomedicines for Ultrasonic Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis.Frontiers in immunology · 2024Review
- Non-Coding RNAs in Human Cancer and Other Diseases: Overview of the Diagnostic Potential.International journal of molecular sciences · 2023Review
- Exosomal miRNA in early-stage hepatocellular carcinoma.World journal of clinical cases · 2023Review
- Hepatocellular carcinoma, hepatitis C virus infection and miRNA involvement: Perspectives for new therapeutic approaches.World journal of gastroenterology · 2022Review
- Review
- Quadruple and Truncated MEK3 Mutants Identified from Acute Lymphoblastic Leukemia Promote Degradation and Enhance Proliferation.International journal of molecular sciences · 2021Article
- Autophagy activity in cholangiocarcinoma is associated with anatomical localization of the tumor.PloS one · 2021Article
- Transcription Factors and Methylation Drive Prognostic miRNA Dysregulation in Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- In Hepatocellular Carcinoma, miRNA-296-3p Targets MSL2 and Suppresses Cell Proliferation and Invasion.Journal of oncology · 2021Article
- lncRNA MSTRG.29039.1 Promotes Proliferation by Sponging hsa-miR-12119 via JAK2/STAT3 Pathway in Multiple Myeloma.Oxidative medicine and cellular longevity · 2021Article
- Sulforaphene inhibits esophageal cancer progression via suppressing SCD and CDH3 expression, and activating the GADD45B-MAP2K3-p38-p53 feedback loop.Cell death & disease · 2020Article
- Ultrasound-mediated delivery of miRNA-122 and anti-miRNA-21 therapeutically immunomodulates murine hepatocellular carcinoma in vivo.Journal of controlled release : official journal of the Controlled Release Society · 2020Article
- Influence of miR-101 on proliferation of liver cancer cells through the MAPK/ERK signaling pathway.Oncology letters · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundmicroRNA 21 (miR-21) has been demonstrated to be significantly elevated in many types of cancers, including the hepatocellular carcinoma (HCC). In the present study, we investigated the role of miR-21 in HCC by identifying its novel targets, as well as its underlying molecular mechanism.
methodsThe expression of mitogen-activated protein kinase-kinase 3 (MAP2K3) in human HCC tumor tissues and adjacent non-tumor tissues was determined by immunohistochemistry staining (IHC) analysis. The 3'-untranslated region (3'-UTR) of MAP2K3 combined with miR-21 was experimentally verified by a miRNA luciferase reporter approach. Moreover, the role of miR-21 in regulating HCC cell proliferation was analyzed by an MTT assay infected with miR-21mimics/sponge inhibitor Adenoviral viral vectors.
resultsBy immunohistochemistry staining analysis, we found that mitogen-activated protein kinase-kinase 3 (MAP2K3) was strikingly repressed in the human HCC tumor tissues, in comparison with the adjacent non-tumor tissues in clinical settings. More importantly, the repression of MAP2K3 was inversely correlated with the expression of miR-21 in HCC. Further study demonstrated that the MAP2K3 was a novel direct target of miR-21, which was experimentally validated by a miRNA luciferase reporter approach. In HepG2 cells, inhibition of miR-21 expression with an adenoviral miR-21 sponge vector profoundly suppressed cell proliferation by up-regulating MAP2K3 expression at both mRNA and protein levels.
conclusionsThese results provide a clinical evidence that MAP2K3 may be a tumor repressor gene, and it is a direct target of miR-21 in HCC, indicating an underlying mechanism by which miR-21 is able to directly target MAP2K3 and inhibit its expression during the carcinogenesis of HCC, at both transcriptional and post-translational levels. This study also suggests that targeting miR-21-MAP2K3 pathway may be a promising strategy in the prevention and treatment of HCC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.