Last update 01 Nov 2024

ILF3

Last update 01 Nov 2024

Basic Info

Synonyms

Double-stranded RNA-binding protein 76, DRBF, DRBP76

+ [24]

Introduction

RNA-binding protein that plays an essential role in the biogenesis of circular RNAs (circRNAs) which are produced by back-splicing circularization of pre-mRNAs. Within the nucleus, promotes circRNAs processing by stabilizing the regulatory elements residing in the flanking introns of the circularized exons. Plays thereby a role in the back-splicing of a subset of circRNAs (PubMed:28625552). As a consequence, participates in a wide range of transcriptional and post-transcriptional processes. Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:14731398). Upon viral infection, ILF3 accumulates in the cytoplasm and participates in the innate antiviral response (PubMed:21123651, PubMed:34110282). Mechanistically, ILF3 becomes phosphorylated and activated by the double-stranded RNA-activated protein kinase/PKR which releases ILF3 from cellular mature circRNAs. In turn, unbound ILF3 molecules are able to interact with and thus inhibit viral mRNAs (PubMed:21123651, PubMed:28625552). (Microbial infection) Plays a positive role in HIV-1 virus production by binding to and thereby stabilizing HIV-1 RNA, together with ILF3.

Drugs associated with ILF3

AQIM-I

Target

ILF3 x survivin

Mechanism

ILF3 modulators [+1]

Active Org.

Shanghai Jiao Tong University

Originator Org.

Shanghai Jiao Tong University

Active Indication

Solid tumor

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ILF3

100 Translational Medicine associated with ILF3

0 Patents (Medical) associated with ILF3

347

Literatures (Medical) associated with ILF3

01 Aug 2024·Advanced Science

Lefamulin Overcomes Acquired Drug Resistance via Regulating Mitochondrial Homeostasis by Targeting ILF3 in Hepatocellular Carcinoma

Article

Author: He, Mengmeng ; Cheng, Yang ; Huang, Shiyu ; Kong, Lingyi ; Ye, Shengtao ; Zheng, Ying ; Wu, Enyi ; Chen, Junxin ; Leng, Yingrong ; Zhang, Hao ; Zhang, Yanqiu

AbstractAcquired resistance represents a critical clinical challenge to molecular targeted therapies such as tyrosine kinase inhibitors (TKIs) treatment in hepatocellular carcinoma (HCC). Therefore, it is urgent to explore new mechanisms and therapeutics that can overcome or delay resistance. Here, a US Food and Drug Administration (FDA)‐approved pleuromutilin antibiotic is identified that overcomes sorafenib resistance in HCC cell lines, cell line‐derived xenograft (CDX) and hydrodynamic injection mouse models. It is demonstrated that lefamulin targets interleukin enhancer‐binding factor 3 (ILF3) to increase the sorafenib susceptibility of HCC via impairing mitochondrial function. Mechanistically, lefamulin directly binds to the Alanine‐99 site of ILF3 protein and interferes with acetyltransferase general control non‐depressible 5 (GCN5) and CREB binding protein (CBP) mediated acetylation of Lysine‐100 site, which disrupts the ILF3‐mediated transcription of mitochondrial ribosomal protein L12 (MRPL12) and subsequent mitochondrial biogenesis. Clinical data further confirm that high ILF3 or MRPL12 expression is associated with poor survival and targeted therapy efficacy in HCC. Conclusively, this findings suggest that ILF3 is a potential therapeutic target for overcoming resistance to TKIs, and lefamulin may be a novel combination therapy strategy for HCC treatment with sorafenib and regorafenib.

01 Aug 2024·Chemosphere

Purifying surface water contaminated with azo dyes using nanofiltration: Interactions between dyes and dissolved organic matter

Article

Author: Siddique, Muhammad Saboor ; Yu, Wenzheng ; Jawaduddin, Mian ; Rashid, Sajid ; Su, Zhaoyang

In this research, the interactions of two azo dyes, Methyl Orange (MO) and Eriochrome Black T (EBT), with dissolved organic matter (DOM) in surface water were studied, emphasizing their removal using nano-filtration membranes (NF-270 and NF-90). High-Performance Size Exclusion Chromatography (HPSEC) findings indicated that the dyes' molecular weight in deionized (DI) water ranged from 500 to 15k Dalton (Da), adjusting peak intensities with Jingmi River (JM) water Beijing. Notably, when dyes were diluted in JM water, ultraviolet (UV₅₃₃ & ₄₆₆, and UV₂₅₄), together with total organic carbon (TOC) parameters, revealed color removal rates of 99.49% (EBT), 94.2% (MO), 87.6% DOM removal, and 86% TOC removal for NF-90. The NF-90 membrane demonstrated a 75% flux decline for 50 mL permeate volume due to its finer pore structure and higher rejection effectiveness. In contrast, the NF-270 membrane showed a 60% decline in flux under the same conditions. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis of dye-treated membranes in JM water revealed that the NF-270 showed a CC bond peak at 1660 cm^-1 across various samples, while analyzing NF-90, the peaks at 1400 cm^-1, 1040 cm^-1, 750 cm^-1, and 620 cm^-1 disappeared for composite sample removal. The hydrophobicity of each membrane is measured by the contact angle (CA), which identified that initial CAs for NF-270 and NF-90 were 46⁰ and 70⁰, respectively, that were rapidly declined but stabilized after a few seconds of processing. Overall, this investigation shows that azo dyes interact with DOM in surface waters and enhance the removal efficiency of NF membranes.

01 Aug 2024·Clinical and Translational Medicine

Single‐cell sequencing combined with spatial transcriptomics reveals that the IRF7 gene in M1 macrophages inhibits the occurrence of pancreatic cancer by regulating lipid metabolism‐related mechanisms

Article

Author: Tian, Xia ; Liu, Meng ; Chen, Mengge ; Zhu, Qingxi ; Zhan, Ting ; Zou, Yanli ; Liu, Jiaxi ; Yang, Xiulin ; Tan, Jie ; Han, Zheng ; Liu, Weijie ; Chen, Mingtao ; Huang, Xiaodong ; Tian, XiaoRong ; Chen, Wei

AbstractAimThe main focus of this study is to explore the molecular mechanism of IRF7 regulation on RPS18 transcription in M1‐type macrophages in pancreatic adenocarcinoma (PAAD) tissue, as well as the transfer of RPS18 by IRF7 via exosomes to PAAD cells and the regulation of ILF3 expression.MethodsBy utilising single‐cell RNA sequencing (scRNA‐seq) data and spatial transcriptomics (ST) data from the Gene Expression Omnibus database, we identified distinct cell types with significant expression differences in PAAD tissue. Among these cell types, we identified those closely associated with lipid metabolism. The differentially expressed genes within these cell types were analysed, and target genes relevant to prognosis were identified. Flow cytometry was employed to assess the expression levels of target genes in M1 and M2 macrophages. Cell lines with target gene knockout were constructed using CRISPR/Cas9 editing technology, and cell lines with target gene knockdown and overexpression were established using lentiviral vectors. Additionally, a co‐culture model of exosomes derived from M1 macrophages with PAAD cells was developed. The impact of M1 macrophage‐derived exosomes on the lipid metabolism of PAAD cells in the model was evaluated through metabolomics analysis. The effects of M1 macrophage‐derived exosomes on the viability, proliferation, division, migration and apoptosis of PAAD cells were assessed using MTT assay, flow cytometry, EdU assay, wound healing assay, Transwell assay and TUNEL staining. Furthermore, a mouse PAAD orthotopic implantation model was established, and bioluminescence imaging was utilised to assess the influence of M1 macrophage‐derived exosomes on the intratumoural formation capacity of PAAD cells, as well as measuring tumour weight and volume. The expression of proliferation‐associated proteins in tumour tissues was examined using immunohistochemistry.ResultsThrough combined analysis of scRNA‐seq and ST technologies, we discovered a close association between M1 macrophages in PAAD samples and lipid metabolism signals, as well as a negative correlation between M1 macrophages and cancer cells. The construction of a prognostic risk score model identified RPS18 and IRF7 as two prognostically relevant genes in M1 macrophages, exhibiting negative and positive correlations, respectively. Mechanistically, it was found that IRF7 in M1 macrophages can inhibit the transcription of RPS18, reducing the transfer of RPS18 to PAAD cells via exosomes, consequently affecting the expression of ILF3 in PAAD cells. IRF7/RPS18 in M1 macrophages can also suppress lipid metabolism, cell viability, proliferation, migration, invasion and intratumoural formation capacity of PAAD cells, while promoting cell apoptosis.ConclusionOverexpression of IRF7 in M1 macrophages may inhibit RPS18 transcription, reduce the transfer of RPS18 from M1 macrophage‐derived exosomes to PAAD cells, thereby suppressing ILF3 expression in PAAD cells, inhibiting the lipid metabolism pathway, and curtailing the viability, proliferation, migration, invasion of PAAD cells, as well as enhancing cell apoptosis, ultimately inhibiting tumour formation in PAAD cells in vivo. Targeting IRF7/RPS18 in M1 macrophages could represent a promising immunotherapeutic approach for PAAD in the future.

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ILF3

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