ArticleOncotarget2017
Down-regulation of salt-inducible kinase 1 (SIK1) is mediated by RNF2 in hepatocarcinogenesis.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- METTL3-Mediated m6A Modification Regulates the Polycomb Repressive Complex 1 Components BMI1 and RNF2 in Hepatocellular Carcinoma Cells.Molecular cancer research : MCR · 2025Article
- Role of SIK1 in tumors: Emerging players and therapeutic potentials (Review).Oncology reports · 2024Review
- Understanding the roles of salt-inducible kinases in cardiometabolic disease.Frontiers in physiology · 2024Review
- Roles of salt‑inducible kinases in cancer (Review).International journal of oncology · 2023Review
- An immune and epigenetics-related scoring model and drug candidate prediction for hepatic carcinogenesis via dynamic network biomarker analysis and connectivity mapping.Computational and structural biotechnology journal · 2023Article
- The Systematic Analyses of RING Finger Gene Signature for Predicting the Prognosis of Patients with Hepatocellular Carcinoma.Journal of oncology · 2022Article
- Construction of cuproptosis-related lncRNAs/mRNAs model and prognostic prediction of hepatocellular carcinoma.American journal of cancer research · 2022Article
- A novel pyroptosis-regulated gene signature for predicting prognosis and immunotherapy response in hepatocellular carcinoma.Frontiers in molecular biosciences · 2022Article
- Ubiquitin-related molecular classification and risk stratification of hepatocellular carcinoma.Molecular therapy oncolytics · 2021Article
- Dysregulation of Wnt/β-catenin signaling by protein kinases in hepatocellular carcinoma and its therapeutic application.Cancer science · 2021Review
- Development and Validation of Epigenetic Modification-Related Signals for the Diagnosis and Prognosis of Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- Identification of a Novel Metastasis-Related miRNAs-Based Signature for Predicting the Prognosis of Hepatocellular Carcinoma.Journal of oncology · 2021Article
- SIKs suppress tumor function and regulate drug resistance in breast cancer.American journal of cancer research · 2021Article
- RNF2 Mediates Hepatic Stellate Cells Activation by Regulating ERK/p38 Signaling Pathway in LX-2 Cells.Frontiers in cell and developmental biology · 2021Article
- The potent roles of salt-inducible kinases (SIKs) in metabolic homeostasis and tumorigenesis.Signal transduction and targeted therapy · 2020Review
- Exosomal miR-130b-3p targets SIK1 to inhibit medulloblastoma tumorigenesis.Cell death & disease · 2020Article
- Article
- Clinical significance of long non-coding RNA DUXAP8 and its protein coding genes in hepatocellular carcinoma.Journal of Cancer · 2020Article
- SIK1 Regulates CRTC2-Mediated Gluconeogenesis Signaling Pathway in Human and Mouse Liver Cells.Frontiers in endocrinology · 2020Article
- Hybrid Mouse Diversity Panel Identifies Genetic Architecture Associated with the Acute Antisense Oligonucleotide-Mediated Inflammatory Response to a 2'-Nucleic acid therapeutics · 2019Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our previous study reported that down-regulation of SIK1 accelerates the growth and invasion of hepatocellular carcinoma (HCC). However, the underlying mechanism leading to SIK1 down-regulation in HCC largely remains to be determined. Herein, we demonstrated that RNF2 expression is negatively correlated with SIK1 levels in HCC tissues. Kaplan-Meier analysis of tumor samples revealed that high RNF2 expression with concurrent low SIK1 expression is associated with poor overall survival. The down-regulation of RNF2 expression in HCC cells significantly reduces tumor cell growth and metastasis, while the simultaneous down-regulation of both RNF2 and SIK1 restores tumor cell growth in vitro and in tumor xenograft models. Mechanistically, we identified RNF2 as an E3 ligase that targets SIK1 for degradation. We further demonstrated that direct physical interaction between RNF2 and SIK1 triggers SIK1 down-regulation in HCC cells. These data suggest that RNF2 is an important upstream negative regulator of SIK1 and that restoration of SIK1 levels induced by loss of RNF2 inhibited HCC cell growth and promoted apoptosis, which may represent a promising therapeutic strategy for HCC treatment.
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Registered trials
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