A human epidermal growth factor receptor 3/heregulin interaction inhibitor aptamer discovered using SELEX

Takumi Yokoyama; Takehiro Ando; Rina Iwamoto; Daisuke Fuji; Mizuki Yamamoto; Takashi Kawakami

doi:10.1016/j.bbrc.2021.03.076

A human epidermal growth factor receptor 3/heregulin interaction inhibitor aptamer discovered using SELEX

Biochem Biophys Res Commun. 2021 May 14:553:148-153. doi: 10.1016/j.bbrc.2021.03.076. Epub 2021 Mar 24.

Authors

Takumi Yokoyama¹, Takehiro Ando¹, Rina Iwamoto¹, Daisuke Fuji², Mizuki Yamamoto³, Takashi Kawakami⁴

Affiliations

¹ Department of Life and Environmental Sciences, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi, 400-8510, Japan.
² Department of Biotechnology, Faculty of Life and Environmental Sciences, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi, 400-8510, Japan.
³ Department of Integrated Applied Life Science, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi, 400-8510, Japan.
⁴ Faculty of Life and Environmental Sciences, Graduate Faculty of Interdisciplinary Research, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi, 400-8510, Japan; JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan. Electronic address: tkawakami@yamanashi.ac.jp.

PMID: 33770580
DOI: 10.1016/j.bbrc.2021.03.076

Abstract

The interaction of human epidermal growth factor receptor 3 (HER3) and heregulin (HRG) is involved in resistance to human epidermal growth factor receptor 2 (HER2)-targeted cancer treatment, such as therapies using anti-HER2 monoclonal antibody. Therefore, inhibition of the HER3/HRG interaction is potentially valuable therapeutic target for cancer treatment. In this study, we used in vitro selection, also known as systematic evolution of ligands by exponential enrichment (SELEX) against the extracellular domain of human HER3, and discovered a novel RNA aptamer. Pull-down and bio-layer interferometry assays showed that RNA aptamer discovered specifically bound to HER3 with a dissociation constant (K_D) of 700 nM. Pull-down assays using chemiluminescence detection also revealed that the HER3-binding RNA aptamer inhibited interactions between HER3 and human HRG. These results indicated that the novel HER3-binding RNA aptamer has potential to be used as basic tool in a range of applications involving HER3/HRG interactions, including research, therapeutic, and diagnostic applications.

Keywords: Aptamer; Cancer; HER3/HRG interaction Inhibitor; Heregulin; Human epidermal growth factor receptor 3; SELEX.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aptamers, Nucleotide / analysis*
Aptamers, Nucleotide / isolation & purification
Base Sequence
ErbB Receptors / antagonists & inhibitors*
ErbB Receptors / metabolism
Humans
Kinetics
Luminescence
Neuregulin-1 / antagonists & inhibitors*
Neuregulin-1 / metabolism*
Protein Binding / drug effects
Receptor, ErbB-3 / antagonists & inhibitors*
Receptor, ErbB-3 / chemistry
Receptor, ErbB-3 / metabolism*
SELEX Aptamer Technique*

Substances

Aptamers, Nucleotide
Neuregulin-1
ERBB3 protein, human
ErbB Receptors
Receptor, ErbB-3