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Paclitaxel-mediated human aryl hydrocarbon receptor mRNA translation by an internal ribosomal entry site-dependent

Wen-Qing Gao1, Jing Ma1, Liu-Liu Sun1

  • 1Laboratory of Molecular Pharmacology, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.

Oncology Reports
|October 20, 2017
PubMed

Insights

The aryl hydrocarbon receptor (AHR) uses an internal ribosome entry site (IRES) for translation. This mechanism is key to how cancer cells respond to chemotherapy drugs like paclitaxel.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • The aryl hydrocarbon receptor (AHR) is a transcription factor involved in dioxin toxicity and tumor development.
  • Understanding AHR's role in cancer cells offers new avenues for cancer prevention and treatment.

Purpose of the Study:

  • To investigate the translation mechanism of AHR mRNA in cancer cells.
  • To identify the role of AHR and its translation in response to chemotherapeutic agents.

Main Methods:

  • Mapping of the AHR 5'-untranslated region (UTR) to identify functional elements.
  • Analysis of AHR expression and internal ribosome entry site (IRES) activity in various cancer cell lines treated with paclitaxel (PTX).
  • Comparison of IRES activity and AHR expression in paclitaxel-sensitive versus paclitaxel-resistant cancer cells.

Main Results:

  • The 5'-UTR of AHR mRNA contains an internal ribosome entry site (IRES).
  • Full-length AHR 5'-UTR is essential for maximal IRES activity.
  • Paclitaxel (PTX) induces AHR expression in ovarian, breast, hepatic, and colorectal cancer cells via an IRES-dependent mechanism.
  • Increased IRES activity and AHR protein levels were observed in PTX-resistant ovarian cancer cells.

Conclusions:

  • AHR translation is regulated by an IRES-dependent mechanism.
  • This IRES-dependent translation plays a significant role in cancer cell responses to paclitaxel treatment.
  • Targeting AHR translation may offer novel therapeutic strategies for chemoresistant cancers.

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