Related Experiment Video

Updated: May 9, 2026

Precise Visualization of Insulin Receptors A and B in Murine Brain with an RNA In Situ Hybridization Assay
08:34

Precise Visualization of Insulin Receptors A and B in Murine Brain with an RNA In Situ Hybridization Assay

Published on: July 15, 2025

Insulin-like growth factor-I receptor is suppressed through transcriptional repression and mRNA destabilization by a

Po-Chen Chu1, Samuel K Kulp, Ching-Shih Chen

  • 1Division of Medicinal Chemistry, College of Pharmacy and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43221, USA and.

Carcinogenesis
|July 19, 2013
PubMed

Insights

Energy restriction and CG-5 suppress prostate cancer growth by regulating the Insulin-like Growth Factor-I Receptor (IGF-IR). The RNA-binding protein HuR stabilizes IGF-IR mRNA, impacting cancer cell response to these agents.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • Energy restriction (ER) and its mimetics show chemopreventive effects against tumors, often involving the Insulin-like Growth Factor-I Receptor (IGF-IR).
  • The precise molecular mechanisms by which ER influences IGF-IR expression and function remain incompletely understood.
  • Prostate cancer cells are a key model for studying ER's impact on IGF-IR.

Purpose of the Study:

  • To elucidate the posttranscriptional regulation of IGF-IR by the RNA-binding protein HuR in prostate cancer cells.
  • To investigate the role of HuR in mediating the effects of the ER-mimetic agent CG-5 on IGF-IR expression.
  • To identify the specific interaction sites and domains of HuR involved in regulating IGF-IR mRNA stability.

Main Methods:

  • Utilized small interfering RNA (siRNA) to silence HuR expression and ectopic expression to overexpress HuR.
  • Employed RNA pull-down and immunoprecipitation assays to determine HuR binding to IGF-IR mRNA.
  • Analyzed the impact of HuR modulation on IGF-IR mRNA and protein levels in prostate cancer cells treated with CG-5.
  • Assessed the role of specific HuR RNA recognition motifs (RRMs) in mediating IGF-IR mRNA stabilization.

Main Results:

  • CG-5 treatment led to the degradation of Sp1 and HuR proteins, contributing to IGF-IR downregulation.
  • HuR silencing decreased IGF-IR expression by reducing mRNA stability.
  • Ectopic HuR expression increased IGF-IR mRNA and protein stability, partially blocking CG-5's suppressive effect.
  • HuR selectively binds to the 3' untranslated region (UTR) of IGF-IR mRNA, with RRMs 2 and 3 being critical for this interaction and subsequent mRNA stabilization.

Conclusions:

  • HuR acts as a novel posttranscriptional regulator of IGF-IR expression by stabilizing its mRNA.
  • This HuR-mediated stabilization of IGF-IR mRNA contributes to the cellular response to energy restriction mimetics like CG-5.
  • The findings highlight a potential therapeutic target for modulating IGF-IR in cancer, consistent with HuR's established oncogenic role in promoting tumor-associated gene expression.

Related Concept Videos

Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
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...
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...