ILF3 promotes gastric cancer proliferation and may be used as a prognostic marker

Liu, Yü; Li, Yong; Zhao, Yijie; Liu, Yang; Fan, Li; Nan, Jun; Zhao, Qun

doi:10.3892/mmr.2019.10229

Cited by 13 publications

(15 citation statements)

References 27 publications

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“…Thus, our data strongly demonstrate a direct interaction between ELDR and ILF3. ILF3 is a nucleotide-binding protein, functions as a transcriptional activator, and regulates the mRNA synthesis of target genes, mRNA stability, primary miRNA processing, translation resulting induction in tumor proliferation, invasion, angiogenesis, and metastasis (Jia et al, 2019;Liu et al, 2019). We examined the consequence of ELDR and ILF3 interaction in ELDR-depleted OSCC by Western blot analysis.…”

Section: Eldr Interacts With Ilf3mentioning

confidence: 99%

Long non‐coding RNA ELDR enhances oral cancer growth by promoting ILF3‐cyclin E1 signaling

et al. 2020

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Oral squamous cell carcinoma (OSCC) is the sixth most common cancer with a 5-year overall survival rate of 50%. Thus, there is a critical need to understand the disease process, and to identify improved therapeutic strategies. Previously, we found the long non-coding RNA (lncRNA) EGFR long non-coding downstream RNA (ELDR) induced in a mouse tongue cancer model; however, its functional role in human oral cancer remained unknown. Here, we show that ELDR is highly expressed in OSCC patient samples and in cell lines. Overexpression of ELDR in normal non-tumorigenic oral keratinocytes induces cell proliferation, colony formation, and PCNA expression. We also show that ELDR depletion reduces OSCC cell proliferation and PCNA expression. Proteomics data identifies the RNA binding protein ILF3 as an interacting partner of ELDR. We further show that the ELDR-ILF3 axis regulates Cyclin E1 expression and phosphorylation of the retinoblastoma (RB) protein. Intratumoral injection of ELDR-specific siRNA reduces OSCC and PDX tumor growth in mice. These findings provide molecular insight into the role of ELDR in oral cancer and demonstrate that targeting ELDR has promising therapeutic potential.

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Section: Eldr Interacts With Ilf3mentioning

confidence: 99%

Long non‐coding RNA ELDR enhances oral cancer growth by promoting ILF3‐cyclin E1 signaling

et al. 2020

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“…Accumulating evidence has shown that ILF3 is abnormally expressed in a series of malignancies, and is involved in tumor proliferation, metastasis, and invasion ( Hu et al, 2013 ; Jiang et al, 2015 ; Liu et al, 2019 ). However, the action and consequence of ILF3 in ESCC are not well elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…The ILF2/ILF3 complex has been reported to participate in multiple cellular processes such as DNA repair and replication ( Shamanna et al, 2011 ), mRNA stabilization ( Jiang et al, 2015 ), transcription ( Tsai et al, 2021 ), translation inhibition ( Nourreddine et al, 2020 ), and micro-RNA biogenesis ( Todaka et al, 2015 ; Higuchi et al, 2016 ). Recently, the role of ILF2 and ILF3 in tumors is emerging, and it has been found that they were involved in the occurrence and development of various types of malignancy, including gastric cancer ( Yin et al, 2017 ; Liu et al, 2019 ), non–small-cell lung cancer ( Ni T. et al, 2015 ; Cheng et al, 2018 ), breast cancer ( Hu et al, 2013 ; Jin et al, 2018 ), and pancreatic carcinoma ( Wan et al, 2015 ; Li et al, 2019 ). Additionally, ILF2 has been reported to be highly expressed in ESCC and suggested to be a prognostic factor for the poor outcome of ESCC patients ( Ni S. et al, 2015 ; Wen-Jian et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Characterization Reveals ILF2 and ILF3 Affected Metabolic Adaptions in Esophageal Squamous Cell Carcinoma

Zhang

Wang

et al. 2021

Front. Mol. Biosci.

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Esophageal cancer (EC) is a common malignant disease in eastern countries. However, a study of the metabolomic characteristics associated with other biological factors in esophageal squamous cell carcinoma (ESCC) is limited. Interleukin enhancer binding factor 2 (ILF2) and ILF3, double-stranded RNA-binding proteins, have been reported to contribute to the occurrence and development of various types of malignancy. Nevertheless, the underlying functions of ILF2 and ILF3 in ESCC metabolic reprogramming have never been reported. This study aimed to contribute to the metabolic characterization of ESCC and to investigate the metabolomic alterations associated with ILF2 and ILF3 in ESCC tissues. Here, we identified 112 differential metabolites, which were mainly enriched in phosphatidylcholine biosynthesis, fatty acid metabolism, and amino acid metabolism pathways, based on liquid chromatography–mass spectrometry and capillary electrophoresis–mass spectrometry approaches using ESCC tissues and paired para-cancer tissues from twenty-eight ESCC patients. In addition, ILF2 and ILF3 expression were significantly elevated in EC tissues compared to the histologically normal samples, and closely associated with PI3K/AKT and MAPK signaling pathways in ESCC. Moreover, in ESCC tissues with a high ILF2 expression, several short-chain acyl-carnitines (C3:0, C4:0, and C5:0) related to the BCAA metabolic pathway and long-chain acyl-carnitines (C14:0, C16:0, C16:0-OH, and C18:0) involved in the oxidation of fatty acids were obviously upregulated. Additionally, a series of intermediate metabolites involved in the glycolysis pathway, including G6P/F6P, F1,6BP, DHAP, G3P, and 2,3BPG, were remarkably downregulated in highly ILF3-expressed ESCC tissues compared with the corresponding para-cancer tissues. Overall, these findings may provide evidence for the roles of ILF2 and ILF3 during the process of ESCC metabolic alterations, and new insights into the development of early diagnosis and treatment for ESCC. Further investigation is needed to clarify the underlying mechanism of ILF2 and ILF3 on acyl-carnitines and the glycolysis pathway, respectively.

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“…ILF3 may function as a transcriptional coactivator, and regulates tumor proliferation and metastasis. ILF3 results in the deterioration of GC by promoting the proliferation of GC cells, and the detection of this protein may be useful in the prognostic prediction of GC patients (39). However, its role in the drug resistance of GC patients remains unclear.…”

Section: A B C Dmentioning

confidence: 99%

Identification of gene signatures and potential therapeutic targets for acquired chemotherapy resistance in gastric cancer patients

Sun¹,

Zhao²,

Yang³

et al. 2021

J Gastrointest Oncol

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Background: Gastric cancer (GC) is the most common type of gastrointestinal cancer, and has been studied extensively. However, resistance to chemotherapeutic agents has become a major problem, leading to treatment failure. This study aimed to investigate the molecular mechanisms mediating acquired resistance to cisplatin and fluorouracil (CF) combination-based chemotherapy in GC patients. Methods:The microarray datasets (GSE14209, GSE30070) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) using the limma package in R/Bioconductor. Possible targets of the DEMs were predicted using miRWalk, and the putative miRNA-mRNA regulatory network was constructed using Cytoscape software. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and proteinprotein interaction (PPI) analyses were then conducted and visualized using the Search Tool for Retrieval of Interacting Genes (STRING) and Cytoscape. The prognostic value of hub genes was revealed by Kaplan-Meier Plotter. The causal relationships and interactions between proteins were displayed using DisNor.Finally, similarity analysis was conducted using the Connectivity Map (CMap) profiles to predict a group of small molecules in GC treatment.Results: A total of 394 DEGs and 31 DEMs were identified after analysis of pre-and post-treatment samples of clinical responders to CF therapy. TM9SF4, hsa-miR-185-5p, and hsa-miR-145-5p were found to be critical in the miRNA-mRNA regulatory network. The DEGs were found to be mainly enriched in the processes of ribonucleoprotein complex assembly, catalytic activity acting on RNA, mitochondrial matrix, and thermogenesis. The DEMs were predominantly found to be involved in single-stranded RNA binding and endoplasmic reticulum lumen. HDAC5, DDX17, ILF3, and SDHC were identified as hub genes in the PPI network. Of these, HDAC5, DDX17, and ILF3 were found to be closely related to the overall survival of GC patients. DisNor identified the first neighbors of the key genes. Furthermore, CMap profiles predicted a group of small molecules, including several histone deacetylase inhibitors (HDACIs), menadione, and mibefradil, which could serve as promising therapeutic agents to reverse acquired resistance to CF therapy.Conclusions: Our findings reveal new targets and alternative therapies to overcome the acquired resistance of GC patients to CF treatment.

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ILF3 promotes gastric cancer proliferation and may be used as a prognostic marker

Cited by 13 publications

References 27 publications

Long non‐coding RNA ELDR enhances oral cancer growth by promoting ILF3‐cyclin E1 signaling

Long non‐coding RNA ELDR enhances oral cancer growth by promoting ILF3‐cyclin E1 signaling

Metabolomic Characterization Reveals ILF2 and ILF3 Affected Metabolic Adaptions in Esophageal Squamous Cell Carcinoma

Identification of gene signatures and potential therapeutic targets for acquired chemotherapy resistance in gastric cancer patients

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