ArticleInternational journal of molecular medicine2019
MicroRNA‑9‑5p downregulates Klf4 and influences the progression of hepatocellular carcinoma via the AKT signaling pathway.
Article in International journal of molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- YOD1 promotes ferroptosis in acute lung injury by deubiquitination of NCOA4.Communications biology · 2025Article
- Alterations of Krüppel-like Factor Signaling and Potential Targeted Therapy for Hepatocellular Carcinoma.Anti-cancer agents in medicinal chemistry · 2025Review
- MicroRNA-mediated Krüppel-like factor 4 upregulation induces alternatively activated macrophage-associated marker and chemokine transcription in 4,4'-methylene diphenyl diisocyanate exposed macrophages.Xenobiotica; the fate of foreign compounds in biological systems · 2024Article
- MicroRNAs in Hepatocellular Carcinoma Pathogenesis: Insights into Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Therapeutic Targeting of Krüppel-Like Factor 4 and Its Pharmacological Potential in Parkinson's Disease: a Comprehensive Review.Molecular neurobiology · 2024Review
- Article
- miR-9-5p expression is associated with vascular invasion and prognosis in hepatocellular carcinoma, and in vitro verification.Journal of cancer research and clinical oncology · 2023Article
- Deubiquitylase YOD1 regulates CDK1 stability and drives triple-negative breast cancer tumorigenesis.Journal of experimental & clinical cancer research : CR · 2023Article
- A miR-9-5p/FOXO1/CPEB3 Feed-Forward Loop Drives the Progression of Hepatocellular Carcinoma.Cells · 2022Article
- Identification and Characterization of MicroRNAs Involving in Initial Sex Differentiation ofBiology · 2022Article
- hsa-miR-9-5p-Mediated TSPAN9 Downregulation Is Positively Related to Both Poor Hepatocellular Carcinoma Prognosis and the Tumor Immune Infiltration.Journal of immunology research · 2022Article
- Current research advances in microRNA-mediated regulation of Krüppel-like factor 4 in cancer: a narrative review.Annals of translational medicine · 2021Review
- Single-cell analysis reveals the intra-tumor heterogeneity and identifies MLXIPL as a biomarker in the cellular trajectory of hepatocellular carcinoma.Cell death discovery · 2021Article
- Epigenetic Regulation of Hepatocellular Carcinoma Progression through the mTOR Signaling Pathway.Canadian journal of gastroenterology & hepatology · 2021Review
- Identification of a Novel Metastasis-Related miRNAs-Based Signature for Predicting the Prognosis of Hepatocellular Carcinoma.Journal of oncology · 2021Article
- Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types.International journal of molecular sciences · 2020Review
- Long Non-Coding RNA (lncRNA) Small Nucleolar RNA Host Gene 15 (SNHG15) Alleviates Osteoarthritis Progression by Regulation of Extracellular Matrix Homeostasis.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- lncRNA MEG3 inhibits the growth of hepatocellular carcinoma cells by sponging miR-9-5p to upregulate SOX11.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2019Article
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
Krüppel‑like factor 4 (Klf4) is a transcriptional factor involved in the progression of hepatocellular carcinoma (HCC). However, the underlying regulatory mechanisms associated with the Klf4 gene as a tumor suppressor in HCC remain unclear. microRNAs (miRNAs or miRs) are a series of small non‑coding RNAs that serve a vital role in regulating gene expression via their influence on protein translation and the associated degradation of mRNA. The mRNA expression levels of the miRNA, miR‑9‑5p, and Klf4 were measured using reverse transcription‑quantitative polymerase chain reaction. The protein expression levels of Klf4, protein kinase B (AKT), phosphorylated (p‑)AKT, mechanistic target of rapamycin (mTOR), p‑mTOR, B cell lymphoma‑2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax) were determined by western blot analysis. Dual luciferase reporter assay was used to confirm a direct interaction between miR‑9‑5p and the 3'‑untranslated region (3'‑UTR) sequence of Klf4. Cell counting kit‑8 assay, wound healing assay, Transwell migration assay and flow cytometric analysis were performed to evaluate the proliferative, migratory and apoptotic capabilities of the HCC cells. In the present study, miR‑9‑5p was revealed to be overexpressed in HCC as a novel upstream gene of Klf4. miR‑9‑5p expression was inversely associated with Klf4 expression in clinical samples. Additionally, Kaplan‑Meier analysis revealed a markedly poor prognosis of HCC in the miR‑9‑5p high‑expression group. Bioinformatics analysis revealed that miR‑9‑5p bound directly to the 3'‑UTR of Klf4, which reduced the expression levels of Klf4. The miR‑9‑5p/Klf4 axis promoted HCC proliferation and migration, and inhibited HCC apoptosis. Furthermore, miR‑9‑5p upregulated the Bcl‑2/Bax protein ratio and activated AKT/mTOR signaling. Taken together, these data demonstrated that the miR‑9‑5p/Klf4 axis was able to promote HCC progression, which may occur via regulation of the AKT signaling pathway, highlighting a potential novel target in HCC treatment.
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