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eIF3c: a potential therapeutic target for cancer

Rafi Emmanuel1, Shiri Weinstein, Dalit Landesman-Milo

  • 1Laboratory of Nanomedicine, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.

Cancer Letters
|April 30, 2013
PubMed

Insights

Targeting the housekeeping gene eIF3c, vital for protein synthesis, shows therapeutic potential against diverse cancers. RNA interference (RNAi) against eIF3c effectively reduced cancer cell proliferation and induced cell death, highlighting its broad applicability.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Nanomedicine

Background:

  • Cancer cells exhibit genomic instability, leading to heterogeneity and therapeutic challenges.
  • Targeting ubiquitously expressed housekeeping genes offers a potential strategy against diverse malignancies.

Purpose of the Study:

  • To investigate the therapeutic potential of the housekeeping gene eIF3c in various cancer cell lines.
  • To evaluate the efficacy of targeting eIF3c using RNA interference (RNAi) approaches.

Main Methods:

  • RNAi-mediated downregulation of eIF3c in five cancer cell lines (NCI-ADR/RES, HeLa, MCF7, HCT116, B16F10).
  • Assessment of global protein synthesis, cell cycle arrest, proliferation, and cell death.
  • Utilized hyaluronan (HA)-coated lipid-based nanoparticles (LNPs) for siRNA delivery in mouse melanoma cells.

Main Results:

  • eIF3c downregulation significantly decreased global protein synthesis and induced polysome run-off.
  • Reduced eIF3c expression led to cell cycle arrest (G0/G1 or G2/M) in a tissue-dependent manner.
  • This resulted in decreased cell proliferation and induced cancer cell death, with successful siRNA delivery via HA-coated LNPs.

Conclusions:

  • The housekeeping gene eIF3c is crucial for translation initiation and cancer cell survival.
  • Targeting eIF3c presents a promising therapeutic strategy for heterogeneous malignancies.
  • Ubiquitously expressed genes like eIF3c are more effective targets than tumor-specific overexpressed genes.

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