ArticleMolecular cancer2022
CircNFIB inhibits tumor growth and metastasis through suppressing MEK1/ERK signaling in intrahepatic cholangiocarcinoma.
Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 107 citations in OpenAlex.
- CircHECTD1 Promotes Cholangiocarcinoma Progression Through Interaction With SFPQ to Induce Autophagy.Cancer science · 2026Article
- Loss of Rab8a-Dependent Tethering of Lipid Droplets to Mitochondria Contributes to Hypoxia-Reoxygenation Injury.MedComm · 2026Article
- ASPDH inhibits the proliferation, migration, and invasion of liver cancer cells by regulating lactate metabolism and the NF-κB/PD-L1 pathway.Clinics (Sao Paulo, Brazil) · 2026Article
- Circular RNAs in cancer: Its biogenesis, functions, relationships with cancer progression, applications in immunotherapy and biomarker potentials.Cancer immunology, immunotherapy : CII · 2026Review
- MiR-362-3p inhibits the proliferation, migration and EMT of gastric cancer cells by regulating the DEP-1/ERK signaling pathway.Scientific reports · 2026Article
- Targeting circGDI2 disrupt HNRNPC-mediated mPORCN stabilization and enhance LGK-974 anti-tumor therapy in hepatocellular carcinoma.Molecular cancer · 2026Article
- Circular RNAs in Endometriosis: from Expression Pattern To Pathogenesis.Cell biochemistry and biophysics · 2026Review
- Arginase 1 promotes hepatic lipogenesis by regulating ERK2/PPARγ signaling in a non-canonical manner.Nature communications · 2026Article
- Review
- Patchouli alcohol triggers autophagic cell death in non-small cell lung cancer cells through targeting GNAI1 to dissociate the GNAI1/ARRB1 complex.International journal of biological sciences · 2026Article
- Mechanisms of Action and Biomarker Potential of ncRNAs in Hepatocellular Carcinoma and Liver Fibrosis: A Review.Analytical cellular pathology (Amsterdam) · 2026Review
- Cigarette smoke-induced circFOXO3 upregulation enhances autophagy-regulated senescence of type II alveolar cells through interacting with E2F1.Tobacco induced diseases · 2026Article
- The functions of circular RNAs and long noncoding RNAs in cholangiocarcinoma.Discover oncology · 2025Review
- Hypomethylation-mediated upregulation of PHOX1 promotes gastric cancer progression via transactivation of NGFR.Cell death discovery · 2025Article
- CircPPP1CB subtype, hsa_circ_0007439, promotes nasopharyngeal carcinoma progression by upregulating KRT1.Discover oncology · 2025Article
- Advances in Multi-Omics Research on Biomarkers of Intrahepatic Cholangiocarcinoma.Current issues in molecular biology · 2025Review
- The diverse roles of circular RNAs in cholangiocarcinoma.Medical oncology (Northwood, London, England) · 2025Review
- An oxidative stress related gene signature predicts prognosis in cholangiocarcinoma.Discover oncology · 2025Article
- ERK1/2 Signaling in Intrahepatic Cholangiocarcinoma: From Preclinical Advances to Therapeutic Strategies.Biology · 2025Review
- The Role and Function of Non-Coding RNAs in Cholangiocarcinoma Invasiveness.Biomedicines · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundConsiderable evidence shows that circular RNAs (circRNAs) play an important role in tumor development. However, their function in intrahepatic cholangiocarcinoma (ICC) metastasis and the underlying mechanisms are incompletely understood.
methodscircNFIB (hsa_circ_0086376, termed as cNFIB hereafter) was identified in human ICC tissues through circRNAs sequencing. The biological role of cNFIB was determined in vitro and in vivo by gain or loss of functional experiments. Fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to analyze the interaction of cNFIB with dual specificity mitogen-activated protein kinase kinase1 (MEK1). Duolink in situ proximity ligation assay (PLA) and coimmunoprecipitation (co-IP) assay were used to investigate the effects of cNFIB on the interaction between MEK1 and mitogen-activated protein kinase 2 (ERK2). Finally, a series of in vitro and in vivo experiments were performed to explore the influences of cNFIB on the anti-tumor activity of trametinib (a MEK inhibitor).
resultscNFIB was significantly down-regulated in human ICC tissues with postoperative metastases. The loss of cNFIB was highly associated with aggressive characteristics and predicted unfavorable prognosis in ICC patients. Functional studies revealed that cNFIB inhibited the proliferation and metastasis of ICC cells in vitro and in vivo. Mechanistically, cNFIB competitively interacted with MEK1, which induced the dissociation between MEK1 and ERK2, thereby resulting in the suppression of ERK signaling and tumor metastasis. Moreover, we found that ICC cells with high levels of cNFIB held the potential to delay the trametinib resistance. Consistently, in vivo and in vitro studies demonstrated that cotreatment with trametinib and lentivirus vector encoding cNFIB showed greater inhibitory effect than isolated trametinib treatment.
conclusionsOur findings identified that cNFIB played a key role in ICC growth and metastasis by regulating MEK1/ERK signaling. Given the efficacy of cNFIB modulation on ICC suppression and trametinib sensitivity, cNFIB appears to be a potential therapeutic molecule for ICC treatment.
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