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Targeting Non-coding RNA Sensitizes Cancer Cells to Drugs

Mo Yang1, John S Schneekloth1

  • 1Chemical Biology Laboratory, National Cancer Institute, Frederick, MD 21702, USA.

Trends in Pharmacological Sciences
|May 25, 2019
PubMed

Insights

Researchers developed a novel small molecule inhibitor targeting primary microRNA (pri-miR)-515. This approach upregulates HER2 protein, enhancing sensitivity to Herceptin in HER2- breast cancer cells.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Primary microRNA (pri-miR)-515 plays a role in regulating protein levels in cancer cells.
  • HER2 protein upregulation can influence breast cancer cell sensitivity to targeted therapies like Herceptin.
  • Selective modulation of disease-relevant proteins is a key strategy in cancer pharmacotherapy.

Purpose of the Study:

  • To investigate the effect of a novel bivalent small molecule inhibitor on pri-miR-515.
  • To determine if inhibiting pri-miR-515 can modulate HER2 protein levels.
  • To assess the potential of this strategy in enhancing sensitivity to Herceptin in HER2- breast cancer.

Main Methods:

  • Development and application of a bivalent small molecule inhibitor targeting pri-miR-515.
  • Analysis of HER2 protein expression levels following pri-miR-515 perturbation.
  • Assessment of HER2- breast cancer cell sensitivity to Herceptin treatment.

Main Results:

  • The bivalent small molecule inhibitor effectively perturbed pri-miR-515.
  • Perturbation of pri-miR-515 led to a significant upregulation of HER2 protein.
  • HER2- breast cancer cells exhibited increased sensitivity to Herceptin treatment.

Conclusions:

  • Targeting pri-miR-515 with small molecule inhibitors is a viable strategy for cancer therapy.
  • Modulating HER2 protein levels via pri-miR-515 inhibition can overcome resistance to Herceptin.
  • This novel pharmacological approach offers selective protein modulation for improved cancer treatment.
Keywords:
HER2HerceptinSK1/S1P pathwaynon-coding RNAsmall molecule

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