Related Experiment Video

Updated: Apr 6, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

3.4K

Antisense oligonucleotide targeting eukaryotic translation initiation factor 4E reduces growth and enhances

S C Thumma1, B A Jacobson1, M R Patel1

  • 1Division of Hematology, Department of Medicine, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.

Cancer Gene Therapy
|August 1, 2015
PubMed

Insights

Targeting eukaryotic translation initiation factor 4E (eIF4E) with an antisense oligonucleotide (ASO) reduced cancer cell growth and increased chemotherapy sensitivity in non-small-cell lung cancer (NSCLC). This eIF4E-silencing therapy shows promise for NSCLC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Elevated eukaryotic translation initiation factor 4E (eIF4E) levels are linked to increased translation of malignancy-related proteins like VEGF, c-Myc, and osteopontin.
  • Non-small-cell lung cancer (NSCLC) exhibits significantly higher eIF4E levels compared to normal lung tissue, suggesting eIF4E as a potential therapeutic target.

Purpose of the Study:

  • To investigate the efficacy of an antisense oligonucleotide (ASO) targeting eIF4E (4EASO) in inhibiting eIF4E expression and its downstream effects in NSCLC cell lines.
  • To evaluate the impact of eIF4E inhibition on NSCLC cell proliferation, cap-dependent complex formation, and sensitivity to gemcitabine chemotherapy.

Main Methods:

  • Utilized eIF4E-specific antisense oligonucleotide (4EASO) to inhibit eIF4E expression in NSCLC cell lines.
  • Assessed changes in eIF4E levels, cap-dependent complex formation, cell proliferation, and expression of oncogenic proteins (VEGF, c-Myc, osteopontin) and β-actin.
  • Determined the effect of 4EASO treatment on NSCLC cell sensitivity to gemcitabine.

Main Results:

  • 4EASO treatment significantly reduced eIF4E levels in NSCLC cells in a dose-dependent manner compared to control ASO.
  • Inhibition of eIF4E led to decreased cap-dependent complex formation, reduced cell proliferation, and enhanced sensitivity to gemcitabine.
  • Repression of eIF4E resulted in decreased expression of oncogenic proteins VEGF, c-Myc, and osteopontin, while β-actin expression remained unaffected.

Conclusions:

  • eIF4E-silencing therapy, using ASOs, effectively reduces oncogenic protein expression and inhibits NSCLC cell proliferation.
  • Targeting eIF4E demonstrates potential as a standalone or combination therapy with chemotherapy for NSCLC.
  • Further investigation in clinical trials is warranted to explore the therapeutic potential of eIF4E-silencing strategies in NSCLC.

More Related Videos

Xenopus laevis as a Model to Identify Translation Impairment10:24

Xenopus laevis as a Model to Identify Translation Impairment

Published on: September 27, 2015

11.2K
Analysis of Translation Initiation During Stress Conditions by Polysome Profiling10:59

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling

Published on: May 19, 2014

18.9K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.1K
Initiation of Translation02:33

Initiation of Translation

Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
40.4K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
69
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.4K
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
8.3K
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.9K