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Sci Rep. 2018 Jul 30;8(1):11413. doi: 10.1038/s41598-018-29633-x.

High-throughput chemical screening to discover new modulators of microRNA expression in living cells by using graphene-based biosensor.

Ryoo SR1,2, Yim Y1,2, Kim YK3, Park IS1, Na HK4, Lee J5, Jang H6, Won C7, Hong S8,9, Kim SY1, Jeon NL10, Song JM11, Min DH12,13,14.

Author information

1
Department of Chemistry, Seoul National University, Seoul, 08826, Republic of Korea.
2
Center for RNA Research, Institute for Basic Sciences (IBS), Seoul National University, Seoul, 08826, Republic of Korea.
3
Carbon Composite Materials Research Center, Korea Institute of Science and Technology (KIST), Jeonbuk, 55324, Republic of Korea.
4
Center for Nano-Bio Measurement, Korea Research Institute of Standards and Science (KRISS), Daejeon, 34113, Republic of Korea.
5
Predictive Toxicology Department, Korea Institute of Toxicology (KIT), Daejeon, 34114, Republic of Korea.
6
Department of Chemistry, Kwangwoon University, 20 Gwangwoon-ro, Nowon-gu, Seoul, 01897, Republic of Korea.
7
Institute of Biotherapeutics Convergence Technology, Lemonex Inc, Seoul, 08826, Republic of Korea.
8
Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
9
Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon, 34141, Republic of Korea.
10
Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul, 08826, South Korea.
11
College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.
12
Department of Chemistry, Seoul National University, Seoul, 08826, Republic of Korea. dalheemin@snu.ac.kr.
13
Center for RNA Research, Institute for Basic Sciences (IBS), Seoul National University, Seoul, 08826, Republic of Korea. dalheemin@snu.ac.kr.
14
Institute of Biotherapeutics Convergence Technology, Lemonex Inc, Seoul, 08826, Republic of Korea. dalheemin@snu.ac.kr.

Abstract

MicroRNAs (miRNAs) are important regulatory RNAs that control gene expression in various biological processes. Therefore, control over the disease-related miRNA expression is important both for basic research and for a new class of therapeutic modality to treat serious diseases such as cancer. Here, we present a high-throughput screening strategy to identify small molecules that modulate miRNA expression in living cells. The screen enables simultaneous monitoring of the phenotypic cellular changes associated with the miRNA expression by measuring quantitative fluorescent signals corresponding to target miRNA level in living cells based on a novel biosensor composed of peptide nucleic acid and nano-sized graphene oxide. In this study, the biosensor based cellular screening of 967 compounds (including FDA-approved drugs, enzyme inhibitors, agonists, and antagonists) in cells identified four different classes of small molecules consisting of (i) 70 compounds that suppress both miRNA-21 (miR-21) expression and cell proliferation, (ii) 65 compounds that enhance miR-21 expression and reduce cell proliferation, (iii) 2 compounds that suppress miR-21 expression and increase cell proliferation, and (iv) 21 compounds that enhance both miR-21 expression and cell proliferation. We further investigated the hit compounds to correlate cell morphology changes and cell migration ability with decreased expression of miR-21.

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